Abstract
Background
Postmenopausal bone loss and decreased physical performance are commonly presented issues. This study aimed through systematic review and meta‐analysis to examine the benefits of adding exercise to medicine/supplements in postmenopausal women.
Methods
A systematic search was conducted of four electronic databases for articles published from inception to December 2023. Clinical controlled trials comparing the effect of additional exercise and medicine/supplements alone in postmenopausal women were included. The outcomes studied were bone mineral density (BMD) and physical performance. The quality of evidence was evaluated by the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE).
Results
Nineteen articles with 1249 participants were included in this study for systematic review and meta‐analysis. The results showed that additional exercise was not associated with significantly improved BMD at the lumbar spine and hip joint compared with medicine/supplements only. However, results of subgroup analysis of exercise types showed a significant improvement in lumbar spine BMD by combining multiple types of exercise training (SMD = 0.37; 95% confidence interval [CI] = 0.01–0.72; p = .04). Furthermore, additional exercise significantly improved lower extremity muscle strength (Standard Mean Difference [SMD] = 1.77; 95% CI = 0.56–2.98; p = .004), Berg's Balance Scale (SMD = 0.72; 95% CI = 0.12–1.32; p = .02), Timed Up and Go (SMD = −1.07; 95% CI = −1.35–−0.78; p < .001), fear of falling (SMD = 1.32; 95% CI = 0.89–1.75; p < .001), and the quality of life (SMD = 1.39; 95% CI = 0.74–2.05; p < .001). The quality level of the evidence was between low to very low.
Conclusions
The significant value of the exercise was demonstrated through enhancing physical performance and quality of life. Moreover, combining various exercise training programs has shown a positive effect on BMD at the lumbar spine. Therefore, for postmenopausal women, combining exercise with medicine/supplements is recommended to further improve physical function and specific areas of BMD. (PROSPERO: CRD42023390633).
INTRODUCTION
Osteoporosis is a concerning issue in postmenopausal women. After menopause, estrogen receptors are activated inefficiently and cause a rapid decrease in bone density and increased fracture risks. Furthermore, proximal femur site bone mineral density (BMD) is favorable for predicting overall fracture, and lumbar spine (LS) BMD is useful for predicting lumbar fracture. 1 Besides decreased BMD, increasing fall risks are also a concern about fracture incidence in postmenopausal women due to dysfunctional physical performance and further decrease their quality of life (QoL). The Berg's Balance Scale (BBS) and Timed Up and Go (TUG) test are commonly used to screen for risk of falls. 2
Osteoporotic medicine is the most effective way to improve BMD to date. There are two types of osteoporotic medicine: anti‐resorptive drugs to reduce bone loss and anabolic agents to induce bone formation. 3 Present research has demonstrated that bisphosphonates, a group of anti‐resorptive drugs, can significantly improve BMD and decrease fracture risks 4 , 5 , 6 , 7 and so do anabolic drugs. 8 , 9 , 10 Supplements have also shown benefits to bone health. A total calcium intake of 1000 to 1500 mg/day and vitamin D of 600 to 800 IU/day is suggested for postmenopausal women to maintain bone density. 5 Isoflavone is structurally similar to estrogen and has been proven beneficial to BMD. 11 , 12 , 13 A marked reduction in plasma antioxidants was also reported in aged osteoporotic women. 14 A negative relationship between BMD and antioxidant serum level has been observed. 15 Therefore, increasing antioxidant intake helps to preserve BMD as well.
Exercise is another approach to improving BMD 16 , 17 , 18 , 19 , 20 and reducing the risk of osteoporosis for postmenopausal women. 21 According to Wolff's law, when mechanoreceptors in bone are activated by an external force, bone remodeling cycle would be facilitated. 22 Frost theory proposed that net bone growth occurred when bone strain exceeds minimum effective strain. 23 On the basis of these principles, exercise may help promote the bone remodeling cycle by prompting bone strain. Resistance exercise, aerobic exercise, and impact exercise have positive effects on specific‐site BMD, respectively. 16 , 17 , 18 , 19 Combining at least two different training types resulted in positive effects on preserving BMD in postmenopausal women at multiple sites. 20
Moreover, exercise training has shown additional value in physical performance. For example, resistance training increased muscle strength 24 , 25 , 26 and decreased fear of falling. 27 , 28 Balance training improved balance ability and decreased fall risks and the number of falls. 27 , 29 Combining multiple types of exercise training can result in benefits on several aspects of physical function and quality of life (QoL) in postmenopausal women. 25 , 26 , 28 , 29 , 30 , 31 Although medication and supplementation have been shown to effectively reduce fracture rates by improving bone strength, their effectiveness in reducing fall rates, another major cause of fracture in older adults, remains questioned. Adding exercise training to medication or supplementation was observed to bring a more extensive improvement in physical performance to postmenopausal women. 25 , 26 , 28 , 29 , 30 , 31
Previous meta‐analyses have reported the effect of medication, supplementation, or exercise on BMD in postmenopausal women. 6 , 20 , 32 , 33 However, it remains unclear whether adding exercise training to osteoporotic medicine/supplements would exert more benefit on both BMD and physical performance. This systematic review and meta‐analysis aimed to answer the effects of adding exercise training to medicine and/or supplements on BMD and physical performance in postmenopausal women by comparing with medicine and/or supplements.
MATERIALS AND METHODS
This systematic review and meta‐analysis followed the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines. 34 The review protocol was registered on PROSPERO (International Prospective Register of Systematic Reviews) (http://www.crd.york.ac.uk/PROSPERO; PROSPERO registration number: CRD42023390633).
Searching strategy
A systematic search in PubMed, Cochrane Library, Web of Science, and Google Scholar electronic databases was conducted for articles published from inception to December 2023. The following keywords were used: “postmenopause” AND “exercise” OR “physical” OR “activity” OR “training” AND “fall” OR “postural stability” OR “balance” OR “strength” OR “mobility” OR “quality of life” AND “bone density” OR “osteoporosis” OR “osteopenia.”
Eligibility criteria and study selection
The research question and the eligibility criteria were framed by the PICOS model. (Population: postmenopausal women, Intervention: combined osteoporotic medicine/supplements and exercise training, Comparison: osteoporotic medicine/supplements, Outcome: BMD and physical performance, and Study design: controlled clinical trial).
This meta‐analysis included studies that fulfilled the following criteria: (1) included postmenopausal women as participants; (2) comparing the effect of medicine/supplements (osteoporotic medicine or supplements) and additional exercise training with medicine/supplements alone; (3) at least one of the following outcomes were measured: BMD (lumbar spine (LS), femoral neck (FN), trochanter (Tr) and total hip), physical performance (BBS, TUG, leg extensor strength, handgrip strength, stability index), QoL (Osteoporosis Assessment Questionnaire [OPAQ] scores or physical functioning scale of 36‐Item Short‐Form Health Survey Questionnaire [SF‐36]); (4) controlled clinical trial design; and (5) study written in English. The exclusion criteria for studies were: (1) letters, case reports, single‐arm studies, systematic reviews, and meta‐analysis; (2) studies with failure to extract available data; (3) duplicate studies; (4) participants had fractures at any sites or cancer; and (5) no intervention was given for the control group.
Titles and abstracts of articles identified by the search strategy were evaluated independently by two of the three researchers (HH.H., CY.C. and WC.C). Abstracts that did not provide sufficient information on inclusion and exclusion criteria were selected for full‐text evaluation. Then, the same reviewers independently evaluated these full‐text articles and selected them according to the eligibility criteria. Disagreements among reviewers were resolved by consensus. If disagreement persisted, a third reviewer (RY.W.) was consulted.
Data extraction
The data extraction was performed independently by two reviewers via a standardized form. Discordance between reviewers was resolved by consensus or by a third reviewer (RY.W.). The following information was extracted from each article: (1) study characteristics, including authors, publication year, study design, and sample size; (2) participant characteristics, including age, postmenopausal year, and BMD status; (3) intervention protocol, including types, intensity, frequency, duration, and total session of exercise and adherence rate; (4) dosages of medicine and supplements; and (5) intervention of the control group. The primary outcomes were the BMD (LS, FN, Tr, and total hip) and physical performance (BBS, TUG, leg extensor strength, handgrip strength, and stability index). Secondary outcomes included QoL (OPAQ and physical functioning scale of SF‐36) and fear of falling (FoF, subdomain of OPAQ).
Quality assessment
The methodological quality of the included studies was assessed by Physiotherapy Evidence Database (PEDro) scale. 35 , 36 Each study was critically appraised by two researchers independently and discussed with a third researcher for consensus if needed. The PEDro was rated from 0 to 10, with a score of 0–3 indicating “poor” quality, 4–5 indicating “fair” quality, 6–8 indicating “good” quality, and 9–10 indicating “excellent” quality.
In addition, the risk of bias was assessed independently by two reviewers according to the Revised Cochrane risk‐of‐bias tool for randomized trials (RoB 2), 37 and disagreements were discussed with a third reviewer. Five items were assessed including randomization process, deviations from intended intervention, missing outcome data, measurement of the outcome, and selection of the reported result. The risk of bias was determined as “low risk,” “high risk,” or “unclear risk” for each item. The results of the risk of bias were presented graphically using Review Manager (RevMan 5.3, Cochrane Collaboration, Nordic Cochrane Center).
The quality of evidence for each outcome with statistical significance was assessed by Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. 38 The level of evidence would be downgraded by one level according to the following factors: risk of bias, inconsistency, indirectness of evidence, imprecision, and publication bias. On the other hand, the evidence would be upgraded a level for any of the following reasons: large effect, dose–response relationship, and all plausible biases only reducing an apparent treatment effect. The four levels of quality of evidence in GRADE are high, moderate, low, or very low. 38
Data analysis
The meta‐analysis was performed by Review Manager 5.4. Outcome measurement data were recorded as mean ± standard deviation (SD), mean change ± SD, or absolute change scores with 95% confidence intervals (CIs). For the included studies that were multi‐arm design, we split the control arm to avoid a unit‐of‐analysis error by dividing up the number of participants in the shared group. 39 The heterogeneity between studies was tested by Cochran's Q test and I 2 values. 40 High heterogeneity between studies was determined when a p value <.10 of Cochran's Q test or I 2 value >50% and a random‐effects model would be adopted. Otherwise, fixed‐model was applied. Publication bias was investigated by performing Egger's regression test for outcomes of interest that included more than 10 data sets. 41 For outcomes with fewer than 10 data sets, publication bias was assessed based on the presence of significant evidence of small‐study effect. 42 A pooled SMD together with a 95% CI was calculated to identify the overall effectiveness of the intervention. An effect size smaller than 0.2 was considered negligible, with value 0.2–0.5 as a small effect, 0.5–0.8 as a medium effect, 0.8–1.3 as a large effect, and >1.3 as a very large effect. 43 A p value <.05 was considered statistically significant. The subgroup analysis was conducted with ‘exercise type’ as the moderator.
RESULTS
Search results
The literature search resulted in 4450 studies. After removing duplicates, a total of 3479 studies were identified. After screening of titles and abstracts, 146 studies were included for full‐text assessment. Finally, 19 articles were included in the meta‐analysis. A flowchart of the study selection is presented in Figure 1.
FIGURE 1.
PRISMA flow chart for the systematic review on the effect of additional exercise training on bone mineral density (BMD) and physical performance in postmenopausal women.
Methodological quality of the included studies
PEDro scores of the included articles are summarized in Table 1. The PEDro scores of these trials ranged from 4 to 8, with a median score of 5 out of 10 (Table 1). All studies satisfied the two criteria: between‐group difference reported, and point estimate and variability reported. 4 , 24 , 25 , 26 , 27 , 28 , 30 , 31 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 Fifteen of the 19 studies (79%) followed randomized allocation. 4 , 24 , 25 , 26 , 27 , 28 , 31 , 44 , 45 , 46 , 47 , 48 , 50 , 51 , 53 Only four trials (21%) reported allocation concealment. 25 , 26 , 46 , 53 Due to the common limitation of exercise intervention, ~80% of the included studies did not blind the participants and personnel. 24 , 25 , 26 , 27 , 28 , 31 , 44 , 45 , 46 , 47 , 49 , 50 , 51 , 53 , 54 However, 10 studies (53%) reported blinding the assessors. 4 , 25 , 26 , 27 , 30 , 46 , 48 , 52 , 53 , 54 A less than 15% dropout rate was reported in 10 studies (53%), 4 , 25 , 27 , 28 , 47 , 48 , 49 , 51 , 52 , 53 and 7 studies (37%) conducted intention‐to‐treat analyses. 4 , 24 , 26 , 31 , 45 , 46 , 52
TABLE 1.
Assessment of the quality of the included studies, Physiotherapy Evidence Database (PEDro) scale profile.
| Article | Eligibility criteria | Randomized allocation a | Concealed allocation a | Baseline similarity a | Blinding participants a | Blinding therapists a | Blinding assessors a | < 15% dropouts a | Intention to treat analysis a | Between‐group comparisons a | Measure of variability a | Total score |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Basat et al., 2013 44 | Y | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 4 |
| Bemben et al., 2000 24 | Y | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 1 | 1 | 5 |
| Bergström et al., 2008 45 | Y | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 1 | 1 | 5 |
| Borba‐Pinheiro et al., 2016 28 | Y | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 1 | 4 |
| Chilibeck et al., 2013 46 | Y | 1 | 1 | 1 | 0 | 0 | 1 | 0 | 1 | 1 | 1 | 7 |
| Chuin et al., 2009 47 | Y | 1 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 1 | 1 | 5 |
| Filipovi et al., 2021 48 | Y | 1 | 0 | 1 | 0 | 1 | 1 | 1 | 0 | 1 | 1 | 7 |
| Hettchen et al., 2021 26 | Y | 1 | 1 | 1 | 0 | 0 | 1 | 0 | 1 | 1 | 1 | 7 |
| Holubiac et al., 2022 49 | Y | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 1 | 1 | 4 |
| Kemmler et al., 2003 30 | Y | 0 | 0 | 1 | 1 | 0 | 1 | 0 | 0 | 1 | 1 | 5 |
| Kerr et al., 2001 50 | Y | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 4 |
| Madureira et al., 2010 27 | N | 1 | 0 | 1 | 0 | 0 | 1 | 1 | 0 | 1 | 1 | 6 |
| Moreira et al., 2014 51 | Y | 1 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 1 | 1 | 5 |
| Nelson et al., 1991 52 | Y | 0 | 0 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 7 |
| Ozsoy‐Unubol et al., 2020 53 | Y | 1 | 1 | 1 | 0 | 0 | 1 | 1 | 0 | 1 | 1 | 7 |
| Sen et al., 2020 31 | Y | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 1 | 1 | 5 |
| Teixeira et al., 2010 25 | Y | 1 | 1 | 1 | 0 | 0 | 1 | 1 | 0 | 1 | 1 | 7 |
| Uusi‐Rasi et al., 2003 4 | Y | 1 | 0 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 8 |
| Yu et al., 2019 54 | Y | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 1 | 1 | 4 |
Abbreviations: Y, Yes, meets the criteria; N, No, does not meet the criteria.
Score 1: fulfilled the criterion; score 0: did not fulfill the criterion.
Risk of bias in the included studies
Figure 2A presented the risks of bias in all included studies. All studies presented a low risk of bias in the measurement of the results and selection of the reported results. 4 , 24 , 25 , 26 , 27 , 28 , 30 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 Seven studies (37%) presented a low risk of bias, 24 , 25 , 26 , 31 , 46 , 51 , 53 five (26%) reported an unclear risk of bias, 27 , 28 , 45 , 47 , 48 and seven (37%) presented a high risk of bias 4 , 30 , 44 , 49 , 50 , 52 , 54 in the randomization process. In bias due to deviations from intended interventions, only one study (5%) reported a low risk of bias, 46 eight studies (42%) presented unclear risks of bias, 24 , 26 , 27 , 28 , 30 , 31 , 45 , 47 and 10 studies (53%) presented a high risk of bias. 4 , 25 , 44 , 48 , 49 , 50 , 51 , 52 , 53 , 54 Five studies (26%) presented a low risk of bias, 26 , 45 , 47 , 49 , 51 three studies (16%) presented unclear risks of bias, 31 , 46 , 50 and 11 studies (58%) presented a high risk of bias 4 , 24 , 25 , 27 , 28 , 30 , 44 , 48 , 52 , 53 , 54 due to missing outcome data. (See Figure 2B for the summary of the risk of bias.)
FIGURE 2.
(A) Risk of bias graph (B) Risk of bias summary.
Characteristics of the included studies
The 19 included studies involved 1249 participants (670 in the experimental groups, 579 in the control groups). 4 , 24 , 25 , 26 , 27 , 28 , 30 , 31 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 Table 2 summarizes the characteristics of included studies and Table 3 summarizes the exercise training and medicine/supplements of the studies. The mean age of the participants ranged from 48 to 79 years. Eleven of the 19 studies recruited postmenopausal women with low bone density (T‐score < −1.0). 25 , 26 , 27 , 28 , 30 , 31 , 44 , 45 , 48 , 49 , 54 All participants were advised to take medicine and/or supplements to increase bone metabolism. Participants in 15 studies 24 , 26 , 27 , 30 , 31 , 44 , 45 , 46 , 47 , 49 , 50 , 51 , 52 , 53 , 54 were treated with supplements, participants in one study were treated with osteoporotic medicine, 25 and participants in three studies were treated with medicine and supplements. 16 , 38 , 50 Three studies investigated aerobic exercise training, 51 , 52 , 54 four studied resistance exercise training, 24 , 44 , 47 , 49 three studied aerobic impact exercise training, 4 , 31 , 44 one studied balance exercise training, 27 and eight studied combined exercise training. 25 , 26 , 30 , 45 , 46 , 48 , 50 , 53 Weekly training duration ranged from 50 to 500 minutes. The intervention period was equal to or less than 24 weeks in half of the included studies, 24 , 25 , 31 , 44 , 47 , 48 , 49 , 51 , 53 , 54 and the intervention period of the remaining studies was at least 40 weeks. 4 , 26 , 27 , 28 , 30 , 45 , 46 , 50 , 52
TABLE 2.
Characteristics of the included studies in the meta‐analysis (n = 19).
| Author/country | BMD of inclusion | Age (years) | Sample size | Outcome measures | ||
|---|---|---|---|---|---|---|
| (T‐score) a | BMD regions of interest | Physical performance | Quality of life | |||
|
Basat et al., 44 /Turkey |
−1 ~ −2.5 |
EG: 55.9 ± 4.9 CG: 56.2 ± 4.0 |
EG: 11 CG: 6 |
LS, FN | ||
|
Basat et al., 44 /Turkey |
−1 ~ −2.5 |
EG: 55.6 ± 2.9 CG: 56.2 ± 4.0 |
EG: 12 CG: 6 |
LS, FN | ||
|
Bemben et al., 24 /USA |
≥ −2.5 |
EG: 50.5 ± 2.0 CG: 52.3 ± 1.4 |
EG: 10 CG: 5 |
LS, FN, Tr, TH | Leg extensor strength | |
|
Bemben et al., 24 /USA |
≥ −2.5 |
EG: 51.9 ± 2.3 CG: 52.3 ± 1.4 |
EG: 7 CG: 3 |
LS, FN, Tr, TH | Leg extensor strength | |
|
Bergström et al., 45 /Sweden |
−1 ~ −3 (with previous forearm fracture) |
EG: 58.9 ± 4.3 CG: 59.6 ± 3.6 |
EG: 48 CG: 44 |
LS, TH | ||
|
Borba‐Pinheiro et al., 28 /Brazil |
≤ −1 |
EG: 56.3 ± 5.2 CG: 55.3 ± 6.8 |
EG: 20 CG: 9 |
FoF b ,OPAQ | ||
|
Borba‐Pinheiro et al., 28 /Brazil |
≤ −1 |
EG: 60.6 ± 7.5 CG: 55.3 ± 6.8 |
EG: 16 CG: 7 |
FoF b ,OPAQ | ||
|
Chilibeck et al., 46 /Canada |
> −2.5 |
EG: 55.8 ± 5.0 CG: 56.7 ± 6.5 |
EG: 72 CG: 76 |
LS, FN, Tr, TH | ||
|
Chuin et al., 47 /Canada |
n. g. |
EG: 66.3 ± 4.0 CG: 65.5 ± 4.5 |
EG: 8 CG: 8 |
LS, FN | ||
|
Filipovi et al. 48 /Serbia |
≤ −2.5 |
EG: 64.40 ± 5.45 CG: 64.20 ± 5.08 |
EG: 47 CG: 49 |
TUG | ||
|
Hettchen et al. 26 /Germany |
−1 ~ −4 |
EG: 53.6 ± 2.0 CG: 54.4 ± 1.6 |
EG: 27 CG: 27 |
LS, TH | Leg extensor strength | |
|
Holubiac et al., 49 /Romania |
≤ −1 |
EG: 56.2 ± 3.2 CG: 56.8 ± 2.3 |
EG: 15 CG: 14 |
LS | ||
|
Kemmler et al., 30 /Germany |
−1 ~ −2.5 |
EG: 55.1 ± 3.3 CG: 55.8 ± 3.1 |
EG: 59 CG: 41 |
LS, FN, TH | Handgrip strength | |
|
Kerr et al., 50 /Australia |
n. g. |
EG: 60 ± 5 CG: 62 ± 6 |
EG: 30 CG: 20 |
LS, FN, Tr, TH | ||
|
Kerr et al., 50 /Australia |
n. g. |
EG: 59 ± 5 CG: 62 ± 6 |
EG: 24 CG: 16 |
LS, FN, Tr, TH | ||
|
Madureira et al., 27 /Brazil |
≤ −2.5 |
EG: 74.57 ± 4.82 CG: 73.40 ± 4.61 |
EG: 30 CG: 30 |
BBS | FoF b | |
|
Moreira et al., 51 /Brazil |
n. g. |
EG: 58.6 ± 6.71 CG: 59.3 ± 6.07 |
EG: 59 CG: 41 |
LS, FN | ||
|
Nelson et al., 52 /America |
n. g. |
EG: 60.2 ± 1.1 CG: 60.2 ± 1.1 |
EG: 9 CG: 9 |
LS, FN | ||
|
Nelson et al., 52 /USA |
n. g. |
EG: 60.2 ± 1.1 CG: 60.2 ± 1.1 |
EG: 9 CG: 9 |
LS, FN | ||
|
Ozsoy‐Unubol et al., 53 /Turkey |
n. g. |
EG: 55.70 ± 4.84 CG: 55.76 ± 5.08 |
EG: 20 CG: 21 |
BBS, Stability index |
||
|
Sen et al., 31 /Turkey |
−2 ~ −3 |
EG: 53.1 ± 4.4 CG: 54.5 ± 6.4 |
EG: 16 CG: 18 |
LS, FN, TH | TUG | |
|
Teixeira et al. 25 /Brazil |
≤ −2.5 |
EG: 63.1 ± 4.53 CG: 62.78 ± 4.87 |
EG: 43 CG: 42 |
BBS, TUG, Leg extensor strength |
Physical functioning c | |
|
Uusi‐Rasi et al., 4 /Finland |
≥ 2.5 |
EG: 53.0 ± 2.8 CG: 54.2 ± 2.4 |
EG: 38 CG: 38 |
Leg extensor strength, Handgrip strength, Stability index | ||
|
Yu et al., 54 /Taiwan |
−1 ~ −2.5 |
EG: 61.5 ± 7.5 CG: 62.5 ± 6.6 |
EG: 40 CG: 40 |
LS, FN | Physical functioning c | |
Abbreviations: BMD, bone mineral density; n. g., not given; EG, experimental group; CG, control group; LS, lumbar spine; FN, femoral neck; Tr, trochanter; TH, total hip; BBS, Berg's Balance Scale; TUG, Timed Get Up and Go; FoF, fear of falling; SF‐36, 36‐Item Short‐Form Health Survey questionnaire; OPAQ, Osteoporosis Assessment Questionnaire.
According to the World Health Organization (WHO), a T‐score below −2.5 (SD) is defined as osteoporosis, a T‐score between −1 and −2.5 SD is defined as osteopenia, and a T‐score above −1 SD is defined as normal bone density.
Subdomain of OPAQ.
Subscale of SF‐36.
TABLE 3.
Description of medicine/supplements and exercise training of the included studies (n = 19).
| Article | Medicine/supplements | Duration/setting of intervention (EG compliance) | Exercise type | Volume (number of sessions per week x minutes per session) | Exercise composition |
|---|---|---|---|---|---|
| Basat et al., 44 |
Ca: 1200 mg/day Vit. D: 800 IU/day |
6 months/Center‐based, Supervised (≥ 60%) |
R Site: L/E, trunk Intensity: RM (n.g.); 1 set of 10 reps |
3 x 60 |
15 min warm‐up: walking, cycling 30–40 min R: ≥9 exercises for whole body 10 min cool‐down: stretching |
| Basat et al., 44 |
Ca: 1200 mg/day Vit. D: 800 IU/day |
6 months/Center‐based, Supervised (≥ 60%) |
Ai: jump rope Intensity: from 10 progress to a maximum of 50 jumps/session (+5 jumps/week) |
3 x 60 |
15 min warm‐up: walking, cycling 30–40 min Ai 10 min cool‐down: stretching |
| Bemben et al., 24 |
Consume Ca ≥1500 mg/day Or Supplemented Ca: 600 mg/day Vit. D: 125 IU/2 days |
6 months/Center‐based, Supervised (87%) |
R Site: U/E, L/E Intensity: 80% of 1RM with 3 sets of 8 reps |
3 x 60 |
10 min warm‐up 45 min R 5 min cool‐down |
| Bemben et al., 24 |
Consume Ca ≥1500 mg/day Or Supplemented Ca: 600 mg/day Vit. D: 125 IU/2 days |
6 months/Center‐based, Supervised (93%) |
R Site: U/E, L/E Intensity: 40% of 1RM with 3 set, 16 reps |
3 x 60 |
10 min warm‐up 45 min R 5 min cool‐down |
|
Bergström et al., 45 |
Ca: n.g. Vit. D: n.g. |
12 months/Center‐based, Supervised (95%) |
A Intensity: participants decided R Site: trunk, U/E, and L/E Intensity: participants decided |
Fast walk: 3 x 30 A + R: 1–2 x 60 |
30 min fast walk 5 min warm‐up 25 min R 25 min A 5 min cool‐down |
| Borba‐Pinheiro et al., 28 |
Osteoporosis: Alendronate: 70 mg/week Vit. D: 5600 IU/day Osteopenia: Vit. D: 5600 IU/day |
13 months/Center‐based, supervised (n.g.) |
R (60 x 3 x 13) Site: U/E, L/E Intensity:
h repetition number respected the principle of inter‐dependence volume x intensity |
3 x 60 |
Warm‐up:10 s stretching for each muscle groups 60 min R Cool‐down: 10 s stretching for each muscle groups |
| Borba‐Pinheiro et al., 28 |
Osteoporosis: Alendronate: 70 mg/week Vit. D: 5600 IU/day Osteopenia: Vit. D: 5600 IU/day |
13 months/Center‐based, supervised (n.g.) |
R Site: U/E, L/E Intensity:
h repetition number respected the principle of inter‐dependence volume x intensity |
2 x 60 |
Warm‐up (10 s stretching for each muscle groups) 60 min R Cool‐down (10 s stretching for each muscle groups) |
|
Chilibeck et al., 46 |
Isoflavone: 165 mg/day Ca: 1200 mg/day Vit. D: 800 IU/day |
2 years/Center‐based, supervised + Home training (74%) |
A: brisk walking Intensity: 70% of age‐predicted hrmax of each participant R Site: trunk, U/E, L/E Intensity: 80% of 1RM for hack squat and bench press, and 8RM for others; with 2 sets of 8 reps |
A: 4 x 20–30 R: 2 x n.g |
Supervised: 20–30 min A R: 14 exercises Home training: 20–30 min A |
|
Chuin et al., 47 |
Vit. C: 1000 mg/day Vit. E: 600 mg/day |
6 months/Center‐based, supervised (n.g.) |
R Site: trunk, U/E, and L/E Intensity: 80% of 1RM with 3 sets of 8 reps |
3 x 60 |
15 min warm‐up: treadmill or cycling, and stretching 45 min R: 8 exercises |
|
Filipovi et al., 48 |
Bisphosphonate: dosage n.g. Ca: 500 mg/day Vit. D: 800–1000 IU/day |
12 weeks/Center‐based, supervised (93%) |
A: rapid walking Intensity: 70% hrmax R Site: U/E and L/E Intensity: weekly progressed
B: tandem/semi‐tandem gait, single‐leg stance, toe and heel walking, with and without eyes opened, on hard and soft ground Intensity: 3 sets of 12–15 reps |
A: 5 x 50–60 R + B: 3x ≈ 70 |
A: 50–60 min A 10 min cool‐down: slow walking R + B: ≈ 10 min warm‐up: stretching 30 min R: short recovery rest between sets of exercises 15 min B 10 min cool‐down |
| Hettchen et al., 26 |
Ca: 1000 mg/day Vit.D: 800 IU/day |
13 months/Center‐based, supervised + Home training (79 ± 12%) |
A + Ai: impact aerobic dance Aerobic intensity:
Impact intensity:
R1: circuit training Site: trunk, U/E, and L/E Intensity:
R2: resistance training machine Site: trunk, U/E, and L/E Intensity: with a varying number of reps, movement velocity, and varying of RM percentage |
High‐intensity training phase: A + Ai + R1: 40 x 2 R2: 60 x 1 Lower intensity training phase: conducting each training protocol once |
High‐intensity training phase:
A + Ai + R1:
R2:
Lower intensity training phase:
10 to 12 weeks of high‐intensity training were interspersed with 4 to 5 weeks of lower intensity exercise training phase. |
| Holubiac et al., 49 | Supplement (alfacalcidol): 0.5 μg/day |
6 months/Center‐based, supervised (100%) |
R Site: trunk, U/E, and L/E Intensity:
|
2 x 60 | 60 min R: 6 or 5 out of 11 exercises |
| Kemmler et al., 30 |
Consume Ca≥1500 mg/day Vit. D ≥ 500 IU/day |
14 months/Center‐based, supervised + Home training (85%) |
A: running Intensity: 75–80% HRmax Ai: jumping Intensity:
R: Site: trunk, U/E, and L/E Intensity: from 50% of 1RM with 2 sets of 20 reps progressed to 70% of 1RM with 2–4 sets of 10 reps and 90% of 1RM with 2–4 sets of 3 reps |
Supervised: 2 x 60–70 Home training: 2 x 25 |
High‐intensity training phase: 15 min A Ai R: ≥9 exercises 8–10 stretching exercise (performed during rest periods of jumping and strength exercises) Lower intensity training phase: n.g. 25 min Home training: elastic band training and rope skipping After 7 months, 12‐week of high‐intensity resistance training were interspersed with 4 to 6 weeks of lower intensity. |
| Kerr et al., 50 | Ca: 600 mg/day |
2 years/Center‐based, supervised (77%) |
A: brisk walk + stationary bike Intensity: (for stationary bike) 40 s at each station at moderate intensity R Site: trunk, U/E, and L/E Intensity: minimal load for 40 s at each station |
1 x 60 |
30 min warm‐up: brisk walk and stretching 30 min R: 9 exercises 40 s x 9 A: stationary bike |
| Kerr et al., 50 | Ca: 600 mg/day |
2 years/Center‐based, supervised (74%) |
A: brisk walk R Site: trunk, U/E, and L/E Intensity: 3 sets of 8 rep with a progressive increase of load |
1 x 60 |
30 min warm‐up: brisk walk and stretching 30 min R: 9 exercises |
| Madureira et al., 27 |
Ca: 1000–1500 mg/day Vit. D: 400–800 IU/day |
40 weeks/Center‐based, supervised (60%) + Home training (77% of participants performed exercise at least once a week) |
B: balancing in dynamic and static positions |
Supervised: 1 x 60 Home: at least 3 x 30 |
Supervised training: 15 min warm‐up: stretching 15 min walking 30 min B Home training: same exercises as B; instructed by a manual |
|
Moreira et al., 51 |
Ca: 500 mg/day Vit. D: 1000 IU/day |
24 weeks/Center‐based, supervised (85%) |
A: aquatic exercise Intensity:
|
3 x 50–60 |
10 min warm‐up 30–40 min A 10 min cool‐down |
| Nelson et al., 52 |
Ca: 831 mg/day Vit. D: 7.1 𝜇g/day |
52 weeks/Center‐based, supervised (90%) |
A: walking Intensity:
|
4 x 50 | 50 min A |
| Nelson et al., 52 |
Ca: 41 mg/day Vit. D: 4.5 𝜇g/day |
52 weeks/Center‐based, supervised (90%) |
A: walking Intensity:
|
4 x 50 |
50 min A |
| Ozsoy‐Unubol et al., 53 | Vit. D: 50000 IU/week |
8 weeks/Home‐based, not supervised (n.g) |
R: core stabilization exercises Site: trunk Intensity: body weight; 2 sets of 10 rep B: side walking, tandem walking, backward walking, cross‐over walking, back leg raise, side leg raise, wall push‐ups, balancing on one leg Intensity: 2 sets of 10 rep |
3 x 60 |
10 min warm‐up: stretching and breathing 40 min R + B 10 min cool‐down: stretching and breathing |
| Sen et al., 31 |
Ca: 1500 mg/day Vit. D: 880 IU/day |
24 weeks/Center‐based, supervised (84%) |
Ai: jump rope Intensity: from 10 progress to a maximum of 60 jumps/session (+5 jumps/week) |
3 x 60 |
20 min warm‐up: cycling, stepping, stretching Ai: two‐legged vertical jumps Cool‐down: relaxation, stretching |
|
Teixeira et al., 25 |
Osteoporosis medication |
18 weeks/Center‐based, supervised (82%) |
B: proprioception and balance exercises Progression:
R Site: L/E Intensity: 50%–80% of 1RM |
2 x n.g. |
5–10 min warm‐up: treadmill and stretching B: proprioception and balance training R: strengthening exercises |
| Uusi‐Rasi et al., 4 |
Alendronate: 5 mg/day Ca: 630 mg/day Vit. D: 400 IU/day |
12 months/Center‐based, supervised (93%) |
Ai: multidirectional jumping Impact intensity: (GFR) 2.1–5.9 times of body weight |
3 x 60 |
15 min warm‐up 20 min Ai 15 min calisthenics 10 min cool‐down |
| Yu et al., 54 |
Ca: 600 mg/day Vit. D: 800 IU/day |
24 weeks/Center‐based, supervised (81%) |
A: aerobic dance Intensity: 50%–70% of each participant's target heart rate |
3 x 60 |
10 min warm‐up: calisthenics and stretching 35 min A 10–15 min cool‐down |
Note: ≈ Approximately.
Abbreviations: A, aerobic training; Ai, aerobic impact training; B, balance training; Ca, calcium; EG, experimental group; GRF, ground reaction force; IU, international unit; HRmax, heart rate maximum; L/E, lower extremity; n.g., not given; R, resistance training; reps, repetition; RM, repetition maximum; TUT, time under tension; U/E, upper extremity; vit., vitamin.
Effects of training on BMD
Lumbar spine (LS)
Seventeen data sets from 13 studies including 839 participants (experimental: 456; control: 383) were analyzed to evaluate the effects of additional exercise on BMD of the LS. 24 , 26 , 30 , 31 , 44 , 45 , 46 , 47 , 49 , 50 , 51 , 52 , 54 There was no significant publication bias based on the Egger's regression (p = .94). The results did not show a significant difference in LS BMD between medicine/supplements and additional exercise groups (SMD = −0.04, 95% CI = −0.46–−0.39; p = .87). Subgroup analysis revealed that combining aerobic training, aerobic impact training, and resistance training could lead to a significant improvement in LS BMD (SMD = 0.37, 95% CI = 0.01–0.72; p = .04) as compared with medicine/supplements (Figure 3A); however, the level of evidence quality was low based on the GRADE evaluation. 26 , 30
FIGURE 3.
Forest plots illustrating the effects of additional exercise on bone mineral density (BMD) (A) Lumbar spine (B) Femoral neck BMD (C) Trochanter BMD (D) Total hip BMD.
Femoral neck (FN)
Fourteen data sets from 10 studies including 664 participants (experimental: 366; control: 298) evaluated the effects of additional exercise on BMD of the FN. 24 , 30 , 31 , 44 , 46 , 47 , 50 , 51 , 52 , 54 There was no significant publication bias based on the Egger's regression (p = .91). The results did not show a significant difference in FN BMD between supplements and additional exercise groups (SMD = 0.11, 95% CI = −0.23–0.45; p = .51). The results of the subgroup analysis did not show significant effects of additional aerobic training, aerobic impact training, resistance training, or combining training on BMD of the FN as compared with medicine/supplements (Figure 3B).
Trochanter (Tr)
Five data sets from three studies including 263 participants (experimental: 143; control: 120) evaluated the effects of additional exercise on BMD at Tr. 24 , 46 , 50 The results did not show a significant difference in Tr BMD between supplements and additional exercise groups (SMD = −0.44, 95% CI = −1.70–0.81; p = .49). The results of subgroup analysis did not show significant effects of additional resistance training or combining training on BMD of the Tr as compared with medicine/supplements (Figure 3C).
Total hip (TH)
Nine data sets from seven studies including 543 participants (experimental: 293; control: 250) evaluated the effects of additional exercise on BMD of the TH. 24 , 26 , 30 , 31 , 45 , 46 , 50 The results did not show a significant difference in TH BMD between supplements and additional exercise groups (SMD = −0.33, 95% CI = −1.32 – 0.65; p = .51) The results of subgroup analysis did not show significant effects of additional resistance training, aerobic impact training, or combining training on BMD of the TH as compared with medicine/supplements (Figure 3D).
Effects of training on physical performance
Postural control (stability index)
Two studies including 117 participants (experimental: 58; control: 59) evaluated the effects of additional exercise on postural control ability. 4 , 53 The results did not show a significant difference in stability index between supplements and additional exercise groups (SMD = −0.08, 95% CI = −0.44–0.29; p = .68). (Figure 4A).
FIGURE 4.
Forest plots illustrating effects of additional exercise on physical performance (A) Postural control stability index (B) Berg's Balance Scale (C) Timed Up and Go test (D) Leg extensor strength (E) Handgrip strength.
Functional balance (BBS)
Three studies including 186 participants (experimental: 93; control: 93) evaluated the effects of additional exercise on functional balance performance. 25 , 27 , 53 The results demonstrated a significant difference in BBS score between supplements and additional exercise groups (SMD = 0.72, 95% CI = 0.12–1.32; p = .02). Based on the GRADE evaluation, the level of quality of evidence was very low (Table 4). According to subgroup analysis, the significant difference between groups seemed to be attributed to additional balance exercise (SMD = 1.12, 95% CI = 0.57–1.67; p < .001), rather than additional resistance and balance exercise (Figure 4B). Based on the GRADE evaluation, the level of quality of evidence was low.
TABLE 4.
Recommendations assessment, development and evaluation (GRADE) evidence profile.
| Outcomes | Certainty assessment | No. of participants | Effect (95% CI) | Certainty g | Comments | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| No. of studies | Study design | Risk of bias | Inconsistency | Indirectness | Imprecision | Publication bias | EG | CG | ||||
| BMD | ||||||||||||
| LS | 13 | CT | Serious a , b | Serious c | Not serious | Serious d | Not serious | 456 | 383 |
SMD = −0.04 (−0.46, 0.39) |
⨁◯◯◯ Very low |
|
| FN | 10 | CT | Serious a , b | Serious c | Not serious | Serious d , e | Not serious | 366 | 298 |
SMD = 0.11 (−0.23, 0.45) |
⨁◯◯◯ Very low |
|
| Tr | 3 | CT | Serious a , b | Serious c | Not serious | Serious d , e | Not serious | 143 | 120 |
SMD = −0.44 (−1.70, 0.81) |
⨁◯◯◯ Very low |
|
| TH | 7 | CT | Serious a , b | Serious c | Not serious | Serious d , e | Not serious | 293 | 250 |
SMD = −0.33 (−1.32, 0.65) |
⨁◯◯◯ Very low |
|
| Physical performance | ||||||||||||
| Stability index | 2 | CT | Serious a , b | Not serious | Not serious | Serious d , e | Not serious | 58 | 59 |
SMD = −0.08 (−0.44, 0.29) |
⨁⨁◯◯ Low |
|
| BBS | 3 | CT | Serious a , b | Serious c | Not serious | Serious e | Not serious | 93 | 93 |
SMD = 0.72 h (0.12, 1.32) |
⨁◯◯◯ Very low |
|
| TUG | 3 | CT | Serious a , b | Not serious | Not serious | Serious e | Not serious | 106 | 109 |
SMD = −1.07 h (−1.35, −0.78) |
⨁⨁◯◯ Low |
|
| Leg extensor strength | 4 | CT | Serious a , b | Serious c | Not serious | Serious e | Serious f , h | 125 | 115 |
SMD = 1.77 h (0.56, 2.98) |
⨁◯◯◯ Very low |
|
| Handgrip strength | 2 | CT | Serious a , b | Serious c | Not serious | Serious d , e | Not serious | 97 | 79 |
SMD = 0.20 (−0.29, 0.68) |
⨁◯◯◯ Very low |
|
| QoL | ||||||||||||
| Physical functioning | 2 | CT | Serious a , b | Serious c | Not serious | Serious d , e | Not serious | 83 | 82 |
SMD = 0.60 (0.01, 1.19) |
⨁◯◯◯ Very low |
|
| OPAQ | 1 | CT | Serious a , b | Not serious | Not serious | Serious d , e | Serious f | 36 | 16 |
SMD = 1.39 h (0.74, 2.05) |
⨁◯◯◯ Very low |
|
| FoF | 2 | CT | Serious a , b | Not serious | Not serious | Serious d , e | Not serious | 66 | 46 |
SMD = 1.32 h (0.89, 1.75) |
⨁⨁◯◯ Low |
|
Abbreviations: BBS, Berg Balance Scale; BMD, bone mineral density; CI, confidence interval; CG, control group; CT, control trial; EG, experimental group; FN, femoral neck; FoF, fear of falling; GRADE, Working Group grades of evidence; LS, lumbar spine; OPAQ, Osteoporosis Assessment Questionnaire; QoL, quality of life; SF‐36, 36‐Item Short‐Form Health Survey Questionnaire; SMD, standardized mean difference; Tr, trochanter; TH, total hip; TUG, Timed Up and Go test.
Included studies lack of concealed allocation.
Included studies lack of blinding of participants and personnel.
A high level of significant heterogeneity.
Low sensitivity due to wide CI.
Total number of participants is less than 800.
Significant in Egger's test or significant evidence of small‐study effect which indicates the presence of publication bias.
Certainty: Moderate, the effect in the study is close to true effect, but it is also possible that it is substantially different; Low, the true effect may be substantially different from the estimate of the effect; Very low, the true effect is likely to be substantially different from the estimate of effect.
Indicates significant differences (p < .05) between groups favoring exercise group.
Mobility (TUG)
Three studies including 215 participants (experimental: 106; control: 109) evaluated the effects of additional exercise on mobility. 25 , 31 , 48 The results demonstrated a significant difference in TUG time between supplements and additional exercise groups (SMD = −1.07, 95% CI = −1.35–−0.78; p < .001) (Figure 4C). Based on the GRADE evaluation, the level of quality of evidence was low (Table 4).
Muscle strength
Five data sets from four studies including 240 participants (experimental: 125; control: 115) evaluated the effects of additional exercise on leg extensor strength. 4 , 24 , 25 , 26 The results showed a significant difference in leg extensor muscle strength between supplements and additional exercise groups (SMD = 1.77, 95% CI = 0.56–2.98; p = .004) (Figure 4D). Based on the GRADE evaluation, the level of quality of evidence was very low (Table 4). The results of subgroup analysis also showed significant effects of additional resistance training (SMD = 2.18, 95% CI = 1.07–3.30; p = .0001); combined resistance and balance training (SMD = 2.22, 95% CI = 1.68–2.77; p < .00001); and combined aerobic, aerobic impact, and resistance training (SMD = 2.45, 95% CI = 1.74–3.17; p < .00001) on leg extensor strength compared with medicine/supplements. Based on the GRADE evaluation, the level of quality of evidence of each exercise type was low. Two studies including 176 participants (experimental: 97; control: 79) evaluated the effects of additional exercise on handgrip strength. 4 , 30 The results did not show a significant difference in handgrip strength between supplements and additional exercise groups (SMD = 0.20, 95% CI = −0.29–0.68; p = .42) (Figure 4E).
Effects of training on QoL
Physical functioning (subscale of SF‐36)
Two studies including 165 participants (experimental: 83; control: 82) evaluated the effects of additional exercise on physical function, a subscale of SF‐36. 25 , 54 The results revealed a trend toward significant difference in physical functioning QoL between supplements and additional exercise groups (SMD = 0.60, 95% CI = 0.01–1.19; p = .05) (Figure 5A).
FIGURE 5.
Forest plots illustrating effects of additional exercise on quality of life (QoL), (A) Physical functioning (subscale of SF‐36) (B) Total scores of Osteoporosis Assessment Questionnaire (OPAQ) (C) Fear of falling (subscale of OPAQ).
Osteoporosis Assessment Questionnaire (OPAQ)
Two data sets extracted from one study including 52 participants (experimental: 36; control: 16) evaluated the effects of additional exercise on QoL. 28 The results revealed a significant difference in OPAQ score between supplements and additional exercise groups (SMD = 1.39; 95% CI = 0.74–2.05; p < .001) (Figure 5B). Based on the GRADE evaluation, the level of quality of evidence was very low (Table 4).
Three data sets from two studies including 112 participants (experimental: 66; control: 46) evaluated the effects of additional exercise on FoF, a subdomain of OPAQ. 27 , 28 The results revealed a significant difference between supplements and additional exercise groups (SMD = 1.32, 95% CI = 0.89–1.75; p < .001). Based on the GRADE evaluation, the level of quality of evidence was low (Table 4). The results of subgroup analysis also showed significant effects of additional exercise training, both balance (SMD = 1.71; 95% CI = 1.11–2.31; p < .001) and resistance exercise (SMD = 0.90; 95% CI = 0.25–1.52; p = .004), on FoF compared with medicine/supplements (Figure 5C). Based on the GRADE evaluation, the level of quality of evidence was low.
DISCUSSION
The meta‐analysis showed that combining exercise and medicine/supplements did not exert more beneficial effects on BMD at LS, FN, Tr, and TH in postmenopausal women. However, adding exercise training to medicine/supplements resulted in a significant improvement in leg extensor strength, BBS score, and TUG test. Such combining programs also improved QoL and FoF. Therefore, additional exercise training showed greater improvement in physical performance in many aspects but not BMD in postmenopausal women.
Although exercise training did not enhance the effects of medicine/supplements on BMD, subgroup analyses of exercise types showed that combining aerobic, aerobic impact, and resistance exercise significantly increased LS BMD. More specifically, combined exercise training that emphasized progressive resistance training may contribute to the greatest improvement. 26 However, this result may not be applied to TH BMD. In line with the meta‐analysis results of Shojaa, training programs that provide joint reaction force have the best effect on LS BMD, and exercises that provide ground reaction force can facilitate the most improvement in TH BMD. 32 Namely, exercise programs that include progressive resistance training on trunk muscles, which may generate more joint reaction force on the LS, seem to have a more positive effect on LS BMD.
There was a negative effect of adding exercise training to isoflavone in the study of Chilibeck et al. on BMD in the LS, FN, Tr, and TH compared to isoflavone alone. 46 The activation of estrogen receptor beta (ER𝛽) may decrease the sensitivity of mechanoreceptors in bone and suppress the effectiveness of bone strain induced by exercise. 55 Consequently, a negative interaction might exist between exercise and isoflavone. We thus performed the sensitivity analysis to eliminate the possible heterogeneous effect. After removing data from the study of Chilibeck et al., the additional exercise exerted more effects on FN BMD than the medicine/supplements intervention (p = .04); however, the results of the subgroup analysis remained insignificant. Hence, whether the types of supplements, such as isoflavone, may influence the additional effects of exercise needs further exploration.
Weakness and risk of fall also caused serious consequences on QoL in postmenopausal women. 56 , 57 , 58 Our results indicated the significant effects of additional exercise training on knee extensor strength, which is important because it is a strong predictor for falls and osteoporotic fractures. 59 According to further subgroup analysis, it seemed that exercise program incorporating resistance training but not aerobic impact exercise could yield positive effects on knee extensor strength. A previous systematic review showed that resistance training at an intensity between 70% and 90% of 1‐RM significantly improved muscle strength. 60 Most of the included studies conducted progressive resistance training of at least 70% of 1‐RM and showed significant improvement in leg extensor strength. 24 , 25 , 26 In addition to load intensity, exercise repetition should be considered. Bemben et al. have shown that both high‐load and low‐repetition, as well as high‐repetition and low‐load resistance training, could significantly improve leg extensor strength. 24 Therefore, types, load, and repetition of exercise training are suggested to be considered to improve knee extensor strength in postmenopausal women. The insignificant finding of hand grip strength was expected because the training programs of the two analyzed studies emphasized aerobic impact exercise of the lower extremities. However, it showed a positive relationship between hand grip strength and functional status in a previous study. 61
The BBS and TUG test are two valid tests for functional balance and mobility, and the scores are frequently used to assess fall risk. 62 Our results show that both BBS and TUG performance improved more after exercise training plus medicine/supplements as compared with medicine/supplements only. However, the results of BBS from the three included studies were not consistent. The exercise programs emphasizing more in balance training exerted greater effects on BBS. 25 , 27 On the other hand, Ozsoy‐Unubol et al. 53 emphasizing both core muscle control and balance training did not demonstrate a significant difference in BBS. Therefore, the training effects on balance performance seem to be task specific. Such task‐specific training for balance control was also noted in the postural control stability index. The two included studies for postural control analysis did not specifically focus on balance training, which may be one of the reasons for the insignificant findings. 4 , 53
Furthermore, the improvement in balance and mobility performance indicated by the TUG test was greater in the additional exercise training groups 25 , 31 , 48 ; however, different exercise programs were noted in these studies. Filipovic et al. adopted combined exercise to include aerobic exercise, resistance exercise, and balance exercise, Teixeira et al. mainly emphasized the balance training, whereas Sen et al. only designed jump rope training as their training exercise. It is known that both balance and mobility are needed for TUG performance; therefore, incorporating these two components in an exercise program might lead to a higher chance to improve the balance and mobility performance in postmenopausal women.
This meta‐analysis demonstrated that additional exercise training two or three times per week could significantly improve QoL in postmenopausal women. 28 We also noted that the additional exercise seemed to improve the ability to perform daily physical tasks subjectively as indicated by physical functioning subscale of SF‐36 (p = .05). Furthermore, FoF, a subdomain of OPAQ, also improved significantly more after adding exercise training, balance training alone, or combined resistance and balance training. 27 , 28 These results were in line with a systematic review that additional exercise training can reduce FoF and increase the QoL. 63 Moreover, Madureira et al. and Swanenburg et al. demonstrated that additional exercise training could significantly decrease the number of falls compared to the medicine/supplement only. 27 , 29
Quality of the evidence
The quality of the evidence was assessed by the GRADE system. 38 Accordingly, level of quality of the evidence ranged from low to very low for all outcomes (Table 4). The level was downgraded by the risk of bias (lack of concealment and blinding procedure), inconsistency (high heterogeneity), imprecision (wide CI and insufficient total number of participants), and publication bias (significant results of Egger's test based on Funnel plot, Figure S1, or significant evidence of small‐study effects). Although the level of the evidence was not high in all outcomes, additional exercise training still showed a significant improvement in functional balance, mobility, leg extensor strength, and QoL. Furthermore, no serious adverse event was reported in the included studies. Thus exercise training is suggested for management of the postmenopausal condition in addition to medicine/supplements.
Limitations
There are several limitations in this systematic review and meta‐analysis. First, the exercise types and protocols of the included studies varied. Comparisons between different types and protocols of exercise programs to enhance the effects of medicine/supplements need further investigation. Second, due to a limited variety of medicine/supplements used in the included studies, the present study did not explore the impact of the interaction between medicine/supplements and exercise. Third, none of the included studies reported the incidence of fracture as one of the outcomes. Hence, it remains unclear whether additional exercise could reduce the risk of fracture. Fourth, only one included study reported the number of falls as their outcome. More research is also needed to establish the effect of exercise on reducing fall incidence in postmenopausal women. Finally, sub‐group analysis of postmenopausal women who may benefit from such exercise was not performed due to insufficient data in the included studies.
CONCLUSION
This systematic review and meta‐analysis found that additional exercise training provided greater improvement in physical performance and QoL, but not in BMD, with low to very low level of evidence. Therefore, exercise training could be suggested to further improve physical performance and QoL in postmenopausal women in addition to medicine/supplements.
DISCLOSURE
The authors declare no conflict of interest.
Supporting information
DATA S1: Supporting Information.
ACKNOWLEDGMENTS
This work was supported by grants from the Ministry of Science and Technology, Taiwan (MOST‐106‐2314‐B‐010‐037‐MY3) and National Health Research Institutes, Taiwan (NHRI‐EX110‐10913PI).
Hsu H‐H, Chiu C‐Y, Chen W‐C, Yang Y‐R, Wang R‐Y. Effects of exercise on bone density and physical performance in postmenopausal women: A systematic review and meta‐analysis. PM&R. 2024;16(12):1358‐1383. doi: 10.1002/pmrj.13206
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REFERENCES
- 1. Leslie WD, Lix LM, Tsang JF, Caetano PA, Manitoba Bone Density P. Single‐site vs multisite bone density measurement for fracture prediction. Arch Intern Med. 2007;167(15):1641‐1647. doi: 10.1001/archinte.167.15.1641 [DOI] [PubMed] [Google Scholar]
- 2. Lusardi MM, Fritz S, Middleton A, et al. Determining risk of falls in community dwelling older adults: a systematic review and meta‐analysis using posttest probability. J Geriatr Phys Ther. 2017;40(1):1‐36. doi: 10.1519/JPT.0000000000000099 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3. Dalal PK, Agarwal M. Postmenopausal syndrome. Indian J Psychiatry. 2015;57(suppl 2):S222‐S232. doi: 10.4103/0019-5545.161483 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4. Uusi‐Rasi K, Kannus P, Cheng S, et al. Effect of alendronate and exercise on bone and physical performance of postmenopausal women: a randomized controlled trial. Bone. 2003;33(1):132‐143. doi: 10.1016/s8756-3282(03)00082-6 [DOI] [PubMed] [Google Scholar]
- 5. Yong E, Logan S. Menopausal osteoporosis: screening, prevention and treatment. Singapore Med J. 2021;62(4):159‐166. doi: 10.11622/smedj.2021036 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6. Dong SL, Jiao Y, Yang HL. Effectiveness of bisphosphonates on bone mineral density in osteopenic postmenopausal women: a systematic review and network meta‐analysis of randomized controlled trials. Medicine (Baltimore). 2021;100(31):e26715. doi: 10.1097/md.0000000000026715 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7. Khosla S, Bilezikian JP, Dempster DW, et al. Benefits and risks of bisphosphonate therapy for osteoporosis. J Clin Endocrinol Metab. 2012;97(7):2272‐2282. doi: 10.1210/jc.2012-1027 [DOI] [PubMed] [Google Scholar]
- 8. Lewiecki EM, Dinavahi RV, Lazaretti‐Castro M, et al. One year of Romosozumab followed by two years of denosumab maintains fracture risk reductions: results of the FRAME extension study. J Bone Miner Res. 2019;34(3):419‐428. doi: 10.1002/jbmr.3622 [DOI] [PubMed] [Google Scholar]
- 9. Kendler DL, Marin F, Zerbini CAF, et al. Effects of teriparatide and risedronate on new fractures in post‐menopausal women with severe osteoporosis (VERO): a multicentre, double‐blind, double‐dummy, randomised controlled trial. Lancet. 2018;391(10117):230‐240. doi: 10.1016/s0140-6736(17)32137-2 [DOI] [PubMed] [Google Scholar]
- 10. Tsai JN, Uihlein AV, Lee H, et al. Teriparatide and denosumab, alone or combined, in women with postmenopausal osteoporosis: the DATA study randomised trial. Lancet. 2013;382(9886):50‐56. doi: 10.1016/s0140-6736(13)60856-9 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11. Lambert MNT, Thybo CB, Lykkeboe S, et al. Combined bioavailable isoflavones and probiotics improve bone status and estrogen metabolism in postmenopausal osteopenic women: a randomized controlled trial. Am J Clin Nutr. 2017;106:153353. doi: 10.3945/ajcn.117.153353 [DOI] [PubMed] [Google Scholar]
- 12. Wong WW, Lewis RD, Steinberg FM, et al. Soy isoflavone supplementation and bone mineral density in menopausal women: a 2‐y multicenter clinical trial. Am J Clin Nutr. 2009;90(5):1433‐1439. doi: 10.3945/ajcn.2009.28001 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13. Zhang X, Liu Y, Xu Q, et al. The effect of soy isoflavone combined with calcium on bone mineral density in perimenopausal Chinese women: a 6‐month randomised double‐blind placebo‐controlled study. Int J Food Sci Nutr. 2020;71(4):473‐481. doi: 10.1080/09637486.2019.1673703 [DOI] [PubMed] [Google Scholar]
- 14. Maggio D, Barabani M, Pierandrei M, et al. Marked decrease in plasma antioxidants in aged osteoporotic women: results of a cross‐sectional study. J Clin Endocrinol Metabol. 2003;88(4):1523‐1527. doi: 10.1210/jc.2002-021496 [DOI] [PubMed] [Google Scholar]
- 15. Zhang J, Hu X, Zhang J. Associations between serum vitamin E concentration and bone mineral density in the US elderly population. Osteoporos Int. 2017;28(4):1245‐1253. doi: 10.1007/s00198-016-3855-5 [DOI] [PubMed] [Google Scholar]
- 16. Martyn‐St James M, Carroll S. High‐intensity resistance training and postmenopausal bone loss: a meta‐analysis. Osteoporos Int. 2006;17(8):1225‐1240. doi: 10.1007/s00198-006-0083-4 [DOI] [PubMed] [Google Scholar]
- 17. Kelley G. Aerobic exercise and lumbar spine bone mineral density in postmenopausal women: a meta‐analysis. J Am Geriatr Soc. 1998;46(2):143‐152. doi: 10.1111/j.1532-5415.1998.tb02530.x [DOI] [PubMed] [Google Scholar]
- 18. Zhao R, Zhao M, Zhang L. Efficiency of jumping exercise in improving bone mineral density among premenopausal women: a meta‐analysis. Sports Med. 2014;44(10):1393‐1402. doi: 10.1007/s40279-014-0220-8 [DOI] [PubMed] [Google Scholar]
- 19. Kitagawa T, Hiraya K, Denda T, Yamamoto S. A comparison of different exercise intensities for improving bone mineral density in postmenopausal women with osteoporosis: a systematic review and meta‐analysis. Bone Rep. 2022;17:101631. doi: 10.1016/j.bonr.2022.101631 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20. Zhao R, Zhang M, Zhang Q. The effectiveness of combined exercise interventions for preventing postmenopausal Bone loss: a systematic review and meta‐analysis. J Orthop Sports Phys Ther. 2017;47(4):241‐251. doi: 10.2519/jospt.2017.6969 [DOI] [PubMed] [Google Scholar]
- 21. Ji J, Hou Y, Li Z, et al. Association between physical activity and bone mineral density in postmenopausal women: a cross‐sectional study from the NHANES 2007–2018. J Orthop Surg Res. 2023;18(1):501. doi: 10.1186/s13018-023-03976-2 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22. Prendergast PJ, Huiskes R. The biomechanics of Wolff's law: recent advances. Ir J Med Sci. 1995;164(2):152‐154. doi: 10.1007/BF02973285 [DOI] [PubMed] [Google Scholar]
- 23. Frost HM. Skeletal structural adaptations to mechanical usage (SATMU): 1. Redefining Wolff's law: the bone modeling problem. Anat Rec. 1990;226(4):403‐413. doi: 10.1002/ar.1092260402 [DOI] [PubMed] [Google Scholar]
- 24. Bemben DA, Fetters NL, Bemben MG, Nabavi N, Koh ET. Musculoskeletal responses to high‐ and low‐intensity resistance training in early postmenopausal women. Med Sci Sports Exerc. 2000;32(11):1949‐1957. doi: 10.1097/00005768-200011000-00020 [DOI] [PubMed] [Google Scholar]
- 25. Teixeira LE, Silva KN, Imoto AM, et al. Progressive load training for the quadriceps muscle associated with proprioception exercises for the prevention of falls in postmenopausal women with osteoporosis: a randomized controlled trial. Osteoporos Int. 2010;21(4):589‐596. doi: 10.1007/s00198-009-1002-2 [DOI] [PubMed] [Google Scholar]
- 26. Hettchen M, von Stengel S, Kohl M, et al. Changes in menopausal risk factors in early postmenopausal Osteopenic women after 13 months of high‐intensity exercise: the randomized controlled ACTLIFE‐RCT. Clin Interv Aging. 2021;16:83‐96. doi: 10.2147/CIA.S283177 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27. Madureira MM, Bonfa E, Takayama L, Pereira RM. A 12‐month randomized controlled trial of balance training in elderly women with osteoporosis: improvement of quality of life. Maturitas. 2010;66(2):206‐211. doi: 10.1016/j.maturitas.2010.03.009 [DOI] [PubMed] [Google Scholar]
- 28. Borba‐Pinheiro CJ, Dantas EH, Vale RG, et al. Resistance training programs on bone related variables and functional independence of postmenopausal women in pharmacological treatment: a randomized controlled trial. Arch Gerontol Geriatr. 2016;65:36‐44. doi: 10.1016/j.archger.2016.02.010 [DOI] [PubMed] [Google Scholar]
- 29. Swanenburg J, de Bruin ED, Stauffacher M, Mulder T, Uebelhart D. Effects of exercise and nutrition on postural balance and risk of falling in elderly people with decreased bone mineral density: randomized controlled trial pilot study. Clin Rehabil. 2007;21(6):523‐534. doi: 10.1177/0269215507075206 [DOI] [PubMed] [Google Scholar]
- 30. Kemmler W, Engelke K, Weineck J, Hensen J, Kalender WA. The erlangen fitness osteoporosis prevention study: a controlled exercise trial in early postmenopausal women with low bone density—first‐year results. Arch Phys Med Rehabil. 2003;84(5):673‐682. doi: 10.1016/s0003-9993(02)04908-0 [DOI] [PubMed] [Google Scholar]
- 31. Sen EI, Esmaeilzadeh S, Eskiyurt N. Effects of whole‐body vibration and high impact exercises on the bone metabolism and functional mobility in postmenopausal women. J Bone Miner Metab. 2020;38(3):392‐404. doi: 10.1007/s00774-019-01072-2 [DOI] [PubMed] [Google Scholar]
- 32. Shojaa M, Von Stengel S, Schoene D, et al. Effect of exercise training on Bone mineral Density in post‐menopausal women: a systematic review and meta‐analysis of intervention studies. Front Physiol. 2020;11:652. doi: 10.3389/fphys.2020.00652 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 33. Kemmler W, Shojaa M, Kohl M, von Stengel S. Effects of different types of exercise on Bone mineral Density in postmenopausal women: a systematic review and meta‐analysis. Calcif Tissue Int. 2020;107(5):409‐439. doi: 10.1007/s00223-020-00744-w [DOI] [PMC free article] [PubMed] [Google Scholar]
- 34. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta‐analyses: the PRISMA statement. PLoS Med. 2009;6(7):e1000097. doi: 10.1371/journal.pmed.1000097 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 35. Sherrington C, Herbert RD, Maher CG, Moseley AM. PEDro A database of randomized trials and systematic reviews in physiotherapy. Man Ther. 2000;5(4):223‐226. doi: 10.1054/math.2000.0372 [DOI] [PubMed] [Google Scholar]
- 36. de Morton NA. The PEDro scale is a valid measure of the methodological quality of clinical trials: a demographic study. Aust J Physiother. 2009;55(2):129‐133. doi: 10.1016/s0004-9514(09)70043-1 [DOI] [PubMed] [Google Scholar]
- 37. Sterne JA, Savović J, Page MJ, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366:l4898. doi: 10.1136/bmj.l4898 [DOI] [PubMed] [Google Scholar]
- 38. Goldet G, Howick J. Understanding GRADE: an introduction. J Evid Based Med. 2013;6(1):50‐54. doi: 10.1111/jebm.12018 [DOI] [PubMed] [Google Scholar]
- 39. Higgins JPT, Eldridge S, Li T. Chapter 23: Including variants on randomized trials. In: Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA, eds. Cochrane Handbook for Systematic Reviews of Interventions version 6.0. Cochrane; 2019:569‐593. http://www.training.cochrane.org/handbook [Google Scholar]
- 40. Huedo‐Medina TB, Sanchez‐Meca J, Marin‐Martinez F, Botella J. Assessing heterogeneity in meta‐analysis: Q statistic or I2 index? Psychol Methods. 2006;11(2):193‐206. doi: 10.1037/1082-989X.11.2.193 [DOI] [PubMed] [Google Scholar]
- 41. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta‐analysis detected by a simple, graphical test. BMJ. 1997;315(7109):629‐634. doi: 10.1136/bmj.315.7109.629 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 42. Guyatt GH, Oxman AD, Montori V, et al. GRADE guidelines: 5. Rating the quality of evidence‐publication bias. J Clin Epidemiol. 2011;64(12):1277‐1282. doi: 10.1016/j.jclinepi.2011.01.011 [DOI] [PubMed] [Google Scholar]
- 43. Sullivan GM, Feinn R. Using effect size—or why the P value is not enough. J Grad Med Educ. 2012;4(3):279‐282. doi: 10.4300/jgme-d-12-00156.1 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 44. Basat H, Esmaeilzadeh S, Eskiyurt N. The effects of strengthening and high‐impact exercises on bone metabolism and quality of life in postmenopausal women: a randomized controlled trial. J Back Musculoskelet Rehabil. 2013;26(4):427‐435. doi: 10.3233/BMR-130402 [DOI] [PubMed] [Google Scholar]
- 45. Bergstrom I, Landgren B, Brinck J, Freyschuss B. Physical training preserves bone mineral density in postmenopausal women with forearm fractures and low bone mineral density. Osteoporos Int. 2008;19(2):177‐183. doi: 10.1007/s00198-007-0445-6 [DOI] [PubMed] [Google Scholar]
- 46. Chilibeck PD, Vatanparast H, Pierson R, et al. Effect of exercise training combined with isoflavone supplementation on bone and lipids in postmenopausal women: a randomized clinical trial. J Bone Miner Res. 2013;28(4):780‐793. doi: 10.1002/jbmr.1815 [DOI] [PubMed] [Google Scholar]
- 47. Chuin A, Labonte M, Tessier D, et al. Effect of antioxidants combined to resistance training on BMD in elderly women: a pilot study. Osteoporos Int. 2009;20(7):1253‐1258. doi: 10.1007/s00198-008-0798-5 [DOI] [PubMed] [Google Scholar]
- 48. Filipovi CT, Lazovi CM, Backovi CA, et al. A 12‐week exercise program improves functional status in postmenopausal osteoporotic women: randomized controlled study. Eur J Phys Rehabil Med. 2021;57(1):120‐130. doi: 10.23736/S1973-9087.20.06149-3 [DOI] [PubMed] [Google Scholar]
- 49. Holubiac IS, Leuciuc FV, Craciun DM, Dobrescu T. Effect of strength training protocol on Bone mineral Density for postmenopausal women with osteopenia/osteoporosis assessed by dual‐energy X‐ray absorptiometry (DEXA). Sensors (Basel). 2022;22(5):1904. doi: 10.3390/s22051904 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 50. Kerr D, Ackland T, Maslen B, Morton A, Prince R. Resistance training over 2 years increases bone mass in calcium‐replete postmenopausal women. J Bone Miner Res. 2001;16(1):175‐181. doi: 10.1359/jbmr.2001.16.1.175 [DOI] [PubMed] [Google Scholar]
- 51. Moreira LD, Fronza FC, Dos Santos RN, et al. The benefits of a high‐intensity aquatic exercise program (HydrOS) for bone metabolism and bone mass of postmenopausal women. J Bone Miner Metab. 2014;32(4):411‐419. doi: 10.1007/s00774-013-0509-y [DOI] [PubMed] [Google Scholar]
- 52. Nelson ME, Fisher EC, Dilmanian FA, Dallal GE, Evans WJ. A 1‐y walking program and increased dietary calcium in postmenopausal women: effects on bone. Am J Clin Nutr. 1991;53(5):1304‐1311. doi: 10.1093/ajcn/53.5.1304 [DOI] [PubMed] [Google Scholar]
- 53. Ozsoy‐Unubol T, Candan Z, Atar E, et al. The effect of vitamin D and exercise on balance and fall risk in postmenopausal women: a randomised controlled study. Int J Clin Pract. 2021;75(12):e14851. doi: 10.1111/ijcp.14851 [DOI] [PubMed] [Google Scholar]
- 54. Yu PA, Hsu WH, Hsu WB, et al. The effects of high impact exercise intervention on bone mineral density, physical fitness, and quality of life in postmenopausal women with osteopenia: a retrospective cohort study. Medicine (Baltimore). 2019;98(11):e14898. doi: 10.1097/MD.0000000000014898 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 55. Khalid AB, Krum SA. Estrogen receptors alpha and beta in bone. Bone. 2016;87:130‐135. doi: 10.1016/j.bone.2016.03.016 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 56. Oh B, Cho B, Choi HC, et al. The influence of lower‐extremity function in elderly individuals' quality of life (QOL): an analysis of the correlation between SPPB and EQ‐5D. Arch Gerontol Geriatr. 2014;58(2):278‐282. doi: 10.1016/j.archger.2013.10.008 [DOI] [PubMed] [Google Scholar]
- 57. Sewo Sampaio PY, Sampaio RA, Coelho Júnior HJ, et al. Differences in lifestyle, physical performance and quality of life between frail and robust Brazilian community‐dwelling elderly women. Geriatr Gerontol Int. 2016;16(7):829‐835. doi: 10.1111/ggi.12562 [DOI] [PubMed] [Google Scholar]
- 58. Romagnoli E, Carnevale V, Nofroni I, et al. Quality of life in ambulatory postmenopausal women: the impact of reduced bone mineral density and subclinical vertebral fractures. Osteoporos Int. 2004;15(12):975‐980. doi: 10.1007/s00198-004-1633-2 [DOI] [PubMed] [Google Scholar]
- 59. Nguyen T, Sambrook P, Kelly P, et al. Prediction of osteoporotic fractures by postural instability and bone density. BMJ. 1993;307(6912):1111‐1115. doi: 10.1136/bmj.307.6912.1111 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 60. De Labra C, Guimaraes‐Pinheiro C, Maseda A, Lorenzo T, Millán‐Calenti JC. Effects of physical exercise interventions in frail older adults: a systematic review of randomized controlled trials. BMC Geriatr. 2015;15:1:154. doi: 10.1186/s12877-015-0155-4 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 61. Rijk JM, Roos PR, Deckx L, Van Den Akker M, Buntinx F. Prognostic value of handgrip strength in people aged 60 years and older: a systematic review and meta‐analysis. Geriatr Gerontol Int. 2016;16(1):5‐20. doi: 10.1111/ggi.12508 [DOI] [PubMed] [Google Scholar]
- 62. Rubenstein LZ. Falls in older people: epidemiology, risk factors and strategies for prevention. Age Ageing. 2006;35(suppl_2):ii37‐ii41. doi: 10.1093/ageing/afl084 [DOI] [PubMed] [Google Scholar]
- 63. Schoene D, Heller C, Aung YN, Sieber CC, Kemmler W, Freiberger E. A systematic review on the influence of fear of falling on quality of life in older people: is there a role for falls? Clin Interv Aging. 2019;14:701‐719. doi: 10.2147/cia.s197857 [DOI] [PMC free article] [PubMed] [Google Scholar]
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