Skip to main content
NCBI home page
NIHPA Author Manuscripts logoLink to NIHPA Author Manuscripts
. Author manuscript; available in PMC: 2022 Aug 16.
Published in final edited form as: J Assoc Nurses AIDS Care. 2017 Oct 4;29(2):330–337. doi: 10.1016/j.jana.2017.09.012

Bone health in people living with HIV: The role of exercise and directions for future research

Joseph D Perazzo 1,*, Allison R Webel 2, Carl J Fichtenbaum 3, Grace A McComsey 4
PMCID: PMC9381277  NIHMSID: NIHMS1826026  PMID: 29103846

People living with HIV (PLWH) are at a three-fold risk for bone loss compared to individuals who are not living with HIV (Yin & Brown, 2016). Low bone mineral density (BMD) in this population is the result of a combination of risk factors, including higher rates of traditional risk factors for bone loss (e.g. aging, steroid use, low BMI, smoking), as well as disease and treatment-specific risk factors (Hileman, Eckard, & McComsey, 2015) (See Figure 1).

Figure 1.

Figure 1

Open in a new tab

Traditional and HIV-Specific Risk Factors for Bone Loss

Their increased risk of bone loss has resulted in a higher incidence of fractures in adults living with HIV (Gonciulea et al., 2017; Sharma et al., 2015), prompting clinician assessment and intervention to improve bone density. To date, the majority of studies and clinical interventions have included pharmacological agents to treat bone loss promote absorption and retention of minerals (e.g. bisphosphonates, Vitamin D supplementation). Pharmacological treatments, while effective, carry an increased risk for side effects (particularly after long term use), and do not address the behavioral and psychosocial contributors to low BMD. Furthermore, failure to address behavioral and psychosocial problems may limit the overall effectiveness of drug therapy, as these problems may affect adherence to medications and further accelerate bone loss. There is a need for a comprehensive approach to treating and preventing bone loss that includes adjuvant self-management and lifestyle strategies in addition to drug therapy (McComsey et al., 2010).

The National Institutes of Health (NIH) Office of AIDS Research has placed high priority on research to promote healthy aging and prevent comorbid conditions in PLWH (National Institutes of Health: Office of AIDS Research, 2016). Increasing physical activity, especially weight bearing aerobic and resistance activity, is a key national health priority (Office of Disease Prevention and Health Promotion, 2017) and an affordable strategy for achieving and maintaining bone health (Weaver et al., 2016). For example, some studies have linked regular physical activity among healthy adults to reduced fracture risk between 30-50% (Singh, 2015). Furthermore, studies in populations at high risk for accelerated bone loss (e.g. postmenopausal women, cancer survivors) have concluded that exercise improves BMD and reduces the risk of fractures (Mendoza et al., 2016; Winters-Stone, Schwartz, & Nail, 2010; Xu, Lombardi, Jiao, & Banfi, 2016). Exercise may produce a similar benefit in PLWH (Bonato et al., 2012; Santos et al., 2015), but few studies have examined its impact on BMD in PLWH. The objectives of this research brief are to: (a) present an overview of bone health and bone loss, (b) describe the relationship between exercise and bone health, (c) discuss the problem of bone loss in PLWH, and (d) present what is currently known about the impact of physical activity for prevention of bone loss in PLWH with implications for future research and intervention development.

Bone Health and Bone Loss

Throughout the lifespan, skeletal health is maintained through the process of bone remodeling, in which weakened, aged, or injured bone is removed, replaced or reinforced with new, healthy bone tissue (US Department of Health and Human Services, 2004). Bone remodeling is primarily executed via osteoclasts (cells that remove weakened bone) and osteoblasts (cells that produce new bone tissue). These bone-dissolving and bone-forming cells are governed by complex signaling pathways mediated by hormones and cytokines that control activation and inhibition of bone remodeling. For example, receptor activator of nuclear kappa B ligand (RANKL) and osteoprotegerin (OPG), are proteins that play a key role in stimulating and inhibiting (respectively) the breakdown of bone. Once a person reaches peak bone mass (the point of skeletal maturation; estimated between 20-30 years of age), osteoblastic activity decreases, leading to gradual bone loss and decreased BMD that occurs as a result of the aging process (US Department of Health and Human Services, 2004). However, certain conditions, such as the chronic inflammation caused by HIV infection (Hileman et al., 2015) or the estrogen-depleted environment seen in women postmenopause (Mendoza et al., 2016), can accelerate bone loss through dysregulation of bone remodeling (e.g, imbalance due to increased RANKL production and suppression of OPG)(Titanji et al., 2014). These environments lead to decreases in BMD (osteopenia/osteoporosis) that place an individual at risk for bone fractures that can be painful and potentially disabling (Weaver et al., 2016).

Exercise and Bone Health

The connection between exercise and bone health is well established (Weaver et al., 2016). Bone remodeling is triggered when bones are challenged with physical activity, a process known as bone ‘loading’. Conversely, when bones are acutely or chronically unchallenged (e.g. bedrest; sedentary lifestyle), bone breakdown occurs, perhaps due to decreased muscular initiation of bone movement and a bone remodeling response to “unloading”, in which unused (therefore “unnecessary”) bone tissue is removed (Chastin, Mandrichenko, Helbostadt, & Skelton, 2014; Yuan et al., 2016). Weight-bearing exercise induces force and pressure on bones that stimulates osteoblastic activity that strengthens and reinforces bone. Research in animal models, healthy adults, pre and post-menopausal adult women, and older adults has shown that moderate to high levels of physical activity can have positive effects on bone. These positive effects include increasing osteoblast differentiation, anti-inflammatory cytokine production, and OPG expression, and also decrease RANKL expression, which may help strengthen bone and prevent bone loss (Chastin et al., 2014; Sañudo et al., 2017 Yuan et al., 2016). Even among populations at high risk for bone loss (e.g. postmenopausal women; those undergoing cancer treatment), people who engage in higher levels physical activity achieve healthier bones and more stable BMD (Keramaris, Malliaropoulos, Padhiar, King, & Maffulli, 2013; Mendoza et al., 2016; Weaver et al., 2016; Xu et al., 2016). This demonstrates that exercise is a necessity for achieving and maintaining bone health across the lifespan, and is particularly important for individuals at risk for accelerated bone loss (Chastin et al., 2014).

Bone Loss in PLWH

The mechanism leading to lower BMD in PLWH has not been identified. Rather, it appears that multiple factors disrupt bone remodeling (Hileman et al., 2015) in PLWH. These factors include factors directly related to HIV infection (e.g. HIV proteins affecting bone marrow production) (Beaupere et al., 2015; Titanji et al., 2014), direct and indirect effects of HIV treatments on bones (Moran, Weitzmann, & Ofotokun, 2016), disproportionately high prevalence of certain traditional risk factors for bone loss, and lifestyle and behavioral factors (Hileman et al., 2015) that contribute to poor bone health.

HIV-associated Pathophysiological Mechanisms:

Recent studies concluded that HIV infection creates a “perfect storm” for bone loss by diminishing the body’s ability to create new osteoblasts while simultaneously promoting the production and activity of osteoblasts. In vitro studies show that HIV proteins (Tat, Nef, Rev) create oxidative stress reactions that disrupt the maturation of stem cells that would eventually become osteoblasts, and promote maturation of stem cells that become osteoclasts (Beaupere et al., 2015). HIV infection leads to chronic immune activation and inflammation. During inflammation, activated immune cells (T and B cells) increase the production of RANKL and diminishes the production of OPG, leaving RANKL unopposed, further accelerating bone loss (Titanji et al., 2014).

HIV Treatment-Associated Bone Loss:

HIV treatments have also been linked to bone loss in PLWH, with an estimated 2-6% decrease in BMD during the first 96 weeks of ART, with the most profound bone loss occurring during the first 24 weeks (Hileman et al., 2015). ART-related bone loss is complex, and the direct effects of ART on bone have been difficult to quantify (Moran et al., 2016). Tenofovir disoproxil fumarate (TDF) has been the most commonly implicated in bone loss, with greater bone loss seen in TDF-containing regimens than regimens that do not contain TDF in PLWH (Hileman et al., 2015). TDF regimens are associated with renal tubular dysfunction that causes phosphate wasting and subsequent hypophosphatemia and osteomalacia. Furthermore, TDF is associated with increased Vitamin D binding protein, resulting in lower levels of serum 1,25-OH(2)D (Vitamin D Deficiency). This deficiency, in turn, increases parathyroid hormone levels resulting in accelerated breakdown of bone and higher serum concentrations of calcium (Havens et al., 2013; Hileman, Overton, & McComsey, 2016) . Protease inhibitors have also been implicated in bone by a possible contribution to mesenchymal stem cell senescence leading to diminished osteoblast production (Moran et al., 2016). It is important to note that accelerated bone loss occurs to varying degrees in PLWH taking ART regardless of their regimen, suggesting potential indirect effects of ART on bone health. In particular, immune reconstitution and activation of T and B-lymphocytes following ART initiation may create conditions (e.g. increased RANKL-mediated osteoclast activation) that accelerate bone loss (Ofotokun et al., 2016).

Increased Prevalence of Traditional, Lifestyle, and Behavioral Risk Factors for Bone Loss in PLWH:

In addition to HIV and HIV treatment-specific risk factors, PLWH have disproportionate rates of traditional and lifestyle risk factors associated with bone loss. For example, men living with HIV tend to have lower BMIs (Grant et al., 2016), are more likely to be vitamin D-deficient (Hileman et al., 2016), more likely to smoke (Reddy et al., 2016) and drink alcohol (Perazzo & Webel, 2016). Furthermore, other clinical disturbances (e.g. fatigue, sleep disorders) and psychosocial issues (e.g. depression, stigma) may increase the likelihood of sedentary behavior in PLWH (Jaggers & Hand, 2016). Thus, addressing HIV infection alone is probably insufficient to correct all the disturbances that might lead to bone loss in PLWH. There is an urgent need for scientists and clinicians to develop interventions that accompany optimal regimens of ART to promote healthy bones in PLWH.

Interventions to Treat and Prevent Bone Loss in PLWH:

The majority of evidence-based interventions to treat and prevent bone loss in PLWH are pharmacological therapies, including bisphosphonates, supplementation, and ART changes. Bisphosphonates (e.g. alendronate, zoledronate) bind to bone tissue and inhibit osteoclast resorption, effectively preventing further bone loss. Bisphosphonates are a well-established treatment strategy for people with osteopenia/osteoporosis who are at risk for fractures, and are the most common method of treating low BMD in PLWH (Negredo & Warriner, 2016). While studies of the long-term efficacy of bisphosphonates are needed, clinical trials examining both oral and injectable bisphosphonates have demonstrated that bisphosphonates provide effective and sustained (up to 5 years with zoledronate) protection against bone loss in PLWH (Negredo & Warriner, 2016).

Vitamin D and calcium supplementation have also been used as strategies to improve BMD in PLWH, particularly in conjunction bisphosphonate therapy (Negredo & Warriner, 2016). Vitamin D mediates the body’s mechanism of absorbing and releasing calcium into and out of the bones. Hileman’s et al. (2016) recent review demonstrates that PLWH are a population at particularly high risk for Vitamin D deficiency due to similar traditional and HIV-specific risk factors associated with bone loss (e.g. low sun exposure due to sedentary lifestyle, HIV medications that interrupt vitamin D metabolism). Clinical trials have demonstrated the promise of Vitamin D supplementation to protect BMD in PLWH and enhance the efficacy of bisphosphonate therapy. Furthermore, vitamin D supplementation may also decrease immune activation, potentially decreasing osteoclast activation (Hileman et al., 2016).

Finally, ART changes have also been proposed for addressing low BMD in PLWH. Recent studies have shown that tenofovir alafenamide fumarate (TAF), a reformulation of TDF, has improved bone outcomes by decreasing serum concentrations leading to more efficient cellular delivery and less bone exposure (De Clercq, 2016). PLWH who are beginning treatment, or those who have experienced bone loss on TDF may benefit from transitioning to TAF as a measure to prevent HIV-related bone loss. These interventions, while effective, may be limited by lifestyle and behavioral factors that lead to accelerated bone loss. Exercise is a health behavioral that has the potential to improve current bone health and prevent further bone loss in PLWH.

Exercise Interventions to Improve Bone Health in PLWH:

Exercise interventions have shown promising outcomes for improving strength, body composition, quality of life, and mental health in PLWH (Jaggers & Hand, 2016; O’Brien, Tynan, Nixon, & Glazier, 2016; Vancampfort et al., 2016). However, few exercise studies have examined bone outcomes in PLWH, and we were unable to identify any completed or ongoing studies examining the effect of physical activity on bone health in PLWH in the gray literature as (as of August 26, 2017). To identify published literature, we searched CINAHL, PubMed, Scopus, and a university electronic journal search engine that pulls articles from more than 1,000 electronic journals to obtain current literature on exercise interventions tested in PLWH that reported bone outcomes. We employed broad search terms including “exercise”; “physical activity”; “HIV”; “Bone”; “Bone Mineral Density”; etc. in various combinations. We reviewed reference lists from obtained articles, and reviewed treatment guidelines for comorbid conditions in PLWH to identify potential studies. Out of more than 60,000 results from the initial search, only two studies examined the effects of exercise interventions on BMD in PLWH. Bonato et al. (2012) tested a 12-week exercise intervention (3 outdoor exercise sessions/week) in 27 virally suppressed PLWH. The sample included men (n=19) and women (n=8) with a median age of 48 years (IQR 43-54) and median CD4+ of 624/ μl (IQR 478-708). ART included PIs (n=13), non-nucleoside reverse transcriptase inhibitors (NNRTIs; n=7), with 15 patients taking TDF. Participants’ general fitness and BMD were measured at baseline and 12 weeks using six-minute walk tests (SMWT), strength exercises (e.g. crunches, chest press, leg extension 1-RM) and dual-energy X-ray absorptiometry (DXA). One group (n=18) completed 60 minutes of brisk walking, while a second group (n=9) completed 60 minutes of walking plus strength training. Spinal BMD scores improved for the entire group (p<0.05) and femoral BMD improved in walking group (p<0.05). Spinal BMD also increased in participants on TDF regimens (n=15), suggesting that exercise may protect against ART-related bone loss (Bonato et al., 2012).

In another study, Santos et al. (2015) tested a 12-week strength training intervention in 20 PLWH who exhibited lipodystrophy, with DXA BMD evaluations at baseline (pre-exercise) and 12 weeks (post-exercise). The sample included men (n=16) and women (n=4) with a mean age of 50.60 (±6.40 years) who reported no regular physical activity practice. Participants were taking ART, including PIs (n=15), Nucleoside reverse transcriptase inhibitors (NRTIs; n=19), and NNRTIs (n=10). Participants completed three 40-minute strength-training sessions weekly (totaling 36 sessions), in which they completed supervised strength exercises (e.g. bench press, lat pull-down, leg extension/flexion, elbow extension/flexion, abdominal exercise), with gradually increasing intensity and varying repetition (see original article by Santos et al. (2015) for full protocol). At the end of the intervention, participants had significant increases in BMD at lumbar spine (3.28%; p=0.012), femoral neck (8.45%; p<0.05), and radius (5.41%; p=0.035; Santos et al., 2015).

DISCUSSION:

We have presented an overview of factors affecting bone health in PLWH and have discussed the potential of exercise as a strategy to promote bone health in this population. We were able to identify only two studies that evaluated the effect of exercise interventions on bone health in samples of PLWH (Bonato et al., 2012; Santos et al., 2015). These studies provide valuable preliminary findings that support the potential impact of exercise as a strategy to prevent bone loss in PLWH. These foundational research findings are consistent with research in other populations at risk for bone loss (e.g. postmenopausal women, cancer patients) that exercise can improve bone health and prevent further bone loss (Mendoza et al., 2016; Winters-Stone et al., 2010; Xu et al., 2016).

More research is needed to address limitations to current knowledge and to develop interventions that integrate behavioral components to strengthen bone and prevent fractures. The studies we identified were limited by small, homogenous samples with little representation from women. Future studies should include larger, representative samples of PLWH to evaluate the overall efficacy of exercise to prevent bone loss in this population. In addition to the need for larger sample sizes to determine efficacy of specific exercises, a greater representation of women will help us understand whether HIV produces an additive risk for bone loss experienced by women post-menopause. Furthermore, greater diversity in future samples will help us determine the degree to which exercise affects bone density across individuals with co-occurring risk factors (e.g. small frame, substance users, various ART regimens etc.). Current studies have also been limited by short observation periods. Future studies should take a prospective, longitudinal approach that will allow a better understanding of the trajectories associated with exercise and changes in bone health over time. Future studies should also consider the impact of exercise interventions early in the HIV treatment plan, as we know that 2-4% of bone mass is lost during the initiation period of ART. The two studies we identified tested controlled aerobic and strength activities. While these interventions provide valuable proof-of-concept data about the impact of exercise on bone health in PLWH, it is important to also measure everyday physical activity leveraging validated objective measures (e.g. self-report, actigraphy). Objective measurement is crucial to understanding activity patterns and sedentary behavior, and will inform researchers about how to appropriately dose exercise interventions in PLWH. Smartphone applications and actigraphs provide avenues for real-time measurement and report of physical activities (Hekler et al., 2015).

The two identified studies measured BMD using DXA, which is the current standard for evaluating BMD and diagnosing osteopenia and osteoporosis. In addition to DXA, future studies can leverage multiple measures of bone health (e.g. traebecular bone scans, bone turnover markers) to measure changes in microarchitecture of bone in response to exercise and evaluate changes in fracture risk (D'Elia, Caracchini, Cavalli, & Innocenti, 2009). Future studies should test tailored exercise interventions that account for symptom experiences as well as psychosocial and financial constraints experienced by PLWH (Jaggers & Hand, 2016). Finally, interventions should be tested in samples of PLWH at different stages of the HIV care continuum to determine the effect of exercise in preventing and mitigating age and HIV-associated health changes across the lifespan.

Exercise interventions are an affordable and sustainable strategy to promote the health of aging PLWH and to mitigate the impact of long-term HIV infection and treatment. When applied in addition to life-sustaining pharmacological treatments, these interventions may be key to delaying or preventing the onset of age-associated comorbid conditions in PLWH who experience accelerated aging in their disease process. Further research and clinical application of exercise interventions will help us take an important step toward promoting healthy aging in PLWH, and achieving national health goals of improved health across populations.

Acknowledgements:

Joseph Perazzo received funding through the National Institute of Nursing Research (NINR) grant #5T32NR014213-03

Footnotes

Disclosures:

The authors report no real or perceived vested interests that relate to this article that could be construed as a conflict of interest.

Contributor Information

Joseph D. Perazzo, University of Cincinnati College of Nursing, Cincinnati, OH USA..

Allison R. Webel, Frances Payne Bolton School of Nursing, Case Western Reserve University, Cleveland, OH USA..

Carl J. Fichtenbaum, University of Cincinnati College of Medicine, Cincinnati, OH, USA..

Grace A. McComsey, Case Western Reserve School of Medicine, Cleveland, OH, USA..

References

  1. Beaupere C, Garcia M, Larghero J, Feve B, Capeau J, & Lagathu C (2015). The HIV proteins Tat and Nef promote human bone marrow mesenchymal stem cell senescence and alter osteoblastic differentiation. Aging Cell. DOI: 10.1111/acel.12308 [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bonato M, Bossolasco S, Galli L, Pavei G, Testa M, Bertocchi C, … Merati G (2012). Moderate aerobic exercise (brisk walking) increases bone density in cART-treated persons. Journal of the International AIDS Society, 15(6). [Google Scholar]
  3. Chastin SF, Mandrichenko O, Helbostadt J, & Skelton DA (2014). Associations between objectively-measured sedentary behaviour and physical activity with bone mineral density in adults and older adults, the NHANES study. Bone, 64, 254–262. DOI: 10.1016/j.bone.2014.04.009 [DOI] [PubMed] [Google Scholar]
  4. D'Elia G, Caracchini G, Cavalli L, & Innocenti P (2009). Bone fragility and imaging techniques. Clinical cases in mineral and bone metabolism, 6(3), 234–246. [PMC free article] [PubMed] [Google Scholar]
  5. De Clercq E (2016). Tenofovir alafenamide (TAF) as the successor of tenofovir disoproxil fumarate (TDF). Biochemical Pharmacology, 119, 1–7. doi: 10.1016/j.bcp.2016.04.015 [DOI] [PubMed] [Google Scholar]
  6. Gonciulea A, Wang R, Althoff KN, Palella FJ, Lake J, Kingsley LA, & Brown TT (2017). An increased rate of fracture occurs a decade earlier in HIV+ compared with HIV− men. AIDS, 31(10), 1435–1443. doi: 10.1097/QAD.0000000000001493. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Grant PM, Kitch D, McComsey GA, Collier AC, Koletar SL, Erlandson KM, … Melbourne K (2016). Long-term bone mineral density changes in antiretroviral-treated HIV-infected individuals. Journal of Infectious Diseases, 214(4), 607–611. doi: 10.1093/infdis/jiw204 [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Havens PL, Kiser JJ, Stephensen CB, Hazra R, Flynn PM, Wilson CM, … Woodhouse LR (2013). Association of higher plasma vitamin D binding protein and lower free calcitriol with tenofovir disoproxil fumarate use and plasma and intracellular tenofovir pharmacokinetics: Cause of a functional vitamin D deficiency? Antimicrobial Agents and Chemotherapy, AAC. 01096–01013. doi: 10.1128/AAC.01096-13 [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hekler EB, Buman MP, Grieco L, Rosenberger M, Winter SJ, Haskell W, & King AC (2015). Validation of physical activity tracking via android smartphones compared to ActiGraph accelerometer: laboratory-based and free-living validation studies. JMIR mHealth and uHealth, 3(2), e36. doi: 10.2196/mhealth.3505 [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hileman CO, Eckard AR, & McComsey GA (2015). Bone loss in HIV—a contemporary review. Current Opinion in Endocrinology, Diabetes, and Obesity, 22(6), 446. doi: 10.1097/MED.0000000000000200 [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hileman CO, Overton ET, & McComsey GA (2016). Vitamin D and bone loss in HIV. Current Opinion in HIV and AIDS, 11(3), 277–284. doi: 10.1097/COH.0000000000000272 [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Jaggers JR, & Hand GA (2016). Health benefits of exercise for people living with HIV: A review of the literature. American Journal of Lifestyle Medicine, 10(3), 184–192. DOI: 10.1177/1559827614538750 [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Keramaris N, Malliaropoulos N, Padhiar N, King J, & Maffulli N (2013). The effect of physical exercise on musculo-skeletal metabolism: A systematic review of the role of rank/rankl/opg pathway. British Journal of Sports Medicine, 47(10), e3–e3. doi: 10.1136/bjsports-2013-092558.38 [DOI] [Google Scholar]
  14. McComsey GA, Tebas P, Shane E, Yin MT, Overton ET, Huang JS, … Brown TT (2010). Bone disease in HIV infection: a practical review and recommendations for HIV care providers. Clinical Infectious Diseases, 51(8), 937–946. doi: 10.1086/656412. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Mendoza N, De Teresa C, Cano A, Godoy D, Hita-Contreras F, Lapotka M, … Ocón O (2016). Benefits of physical exercise in postmenopausal women. Maturitas, 93, 83–88. doi: 10.1016/j.maturitas.2016.04.017 [DOI] [PubMed] [Google Scholar]
  16. Moran CA, Weitzmann MN, & Ofotokun I (2016). The protease inhibitors and HIV-associated bone loss. Current Opinion in HIV and AIDS, 11(3), 333–342. doi: 10.1097/COH.0000000000000260 [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. National Institutes of Health: Office of AIDS Research. (2016). NIH HIV/AIDS Priorities and Guidelines for Determining AIDS Funding. Retrieved from https://grants.nih.gov/grants/guide/notice-files/NOT-OD-15-137.html
  18. Negredo E, & Warriner AH (2016). Pharmacologic approaches to the prevention and management of low bone mineral density in HIV-infected patients. Current Opinion in HIV and AIDS, 11(3), 351–357. doi: 10.1097/COH.0000000000000271. [DOI] [PubMed] [Google Scholar]
  19. O’Brien KK, Tynan A-M, Nixon SA, & Glazier RH (2016). Effectiveness of aerobic exercise for adults living with HIV: systematic review and meta-analysis using the Cochrane Collaboration protocol. BMC Infectious Diseases, 16(1), 182. doi: 10.1186/s12879-017-2342-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Office of Disease Prevention and Health Promotion. (2017). Physical Activity. Healthy People 2020. Retrieved from https://www.healthypeople.gov/2020/topics-objectives/topic/physical-activity
  21. Ofotokun I, Titanji K, Vunnava A, Roser-Page S, Vikulina T, Villinger F, … Lennox JL (2016). Antiretroviral therapy induces a rapid increase in bone resorption that is positively associated with the magnitude of immune reconstitution in HIV infection. AIDS, 30(3), 405–414. doi: 10.1097/QAD.0000000000000918. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Perazzo J, Webel A. Alcohol use and HIV self-management. Journal of the Association of Nurses in AIDS Care. 2017;28(2):295–299. DOI: 10.1016/j.jana.2016.02.006 [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Reddy KP, Parker RA, Losina E, Baggett TP, Paltiel AD, Rigotti NA, … Walensky RP (2016). Impact of cigarette smoking and smoking cessation on life expectancy among people with HIV: A US-based modeling study. Journal of Infectious Diseases, jiw430. doi: 10.1093/infdis/jiw430 [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Santos WR, Santos WR, Paes PP, Ferreira-Silva IA, Santos AP, Vercese N, … Navarro AM (2015). Impact of strength training on bone mineral density in patients infected with HIV exhibiting lipodystrophy. The Journal of Strength & Conditioning Research, 29(12), 3466–3471. doi: 10.1519/JSC.0000000000001001. [DOI] [PubMed] [Google Scholar]
  25. Sañudo B, de Hoyo M, del Pozo-Cruz J, Carrasco L, del Pozo-Cruz B, Tejero S, & Firth E (2017). A systematic review of the exercise effect on bone health: the importance of assessing mechanical loading in perimenopausal and postmenopausal women. Menopause (2017 May 22). doi: 10.1097/GME.0000000000000872. [DOI] [PubMed] [Google Scholar]
  26. Sharma A, Shi Q, Hoover DR, Anastos K, Tien PC, Young MA, … Yin MT (2015). Increased Fracture Incidence in Middle-Aged HIV-Infected and HIV-Uninfected Women: Updated Results From the Women's Interagency HIV Study. Journal of Acquired Immune Deficiency Syndromes, 70(1), 54–61. doi: 10.1097/QAI.0000000000000674. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Singh MAF (2015). Exercise and bone health. In Holick MFN, J.W., (Ed.), Nutrition and Bone Health (pp. 504–542). New York Heidelberg Dordrecht London Springer. [Google Scholar]
  28. Titanji K, Vunnava A, Sheth AN, Delille C, Lennox JL, Sanford SE, … Weitzmann MN (2014). Dysregulated B Cell Expression of RANKL and OPG Correlates with loss of bone mineral density in HIV infection. PLoS Pathog, 2014 Nov, 10(11). doi: 10.1371/journal.ppat.1004497. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. US Department of Health and Human Services. (2004). Bone health and osteoporosis: a report of the Surgeon General. Rockville, MD: US Department of Health and Human Services, Office of the Surgeon General, 87. [Google Scholar]
  30. Vancampfort D, Mugisha J, De Hert M, Probst M, Firth J, Gorczynski P, & Stubbs B (2016). Global physical activity levels among people living with HIV: a systematic review and meta-analysis. Disability and Rehabilitation, 2016 Dec 8 1–10. doi: 10.1080/09638288.2016.1260645 [DOI] [PubMed] [Google Scholar]
  31. Weaver C, Gordon C, Janz K, Kalkwarf H, Lappe J, Lewis R, … Zemel B (2016). The National Osteoporosis Foundation’s position statement on peak bone mass development and lifestyle factors: a systematic review and implementation recommendations. Osteoporosis International, 27(4), 1281–1386. doi: 10.1007/s00198-015-3440-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Winters-Stone KM, Schwartz A, & Nail LM (2010). A review of exercise interventions to improve bone health in adult cancer survivors. Journal of Cancer Survivorship, 4(3), 187–201. doi: 10.1007/s11764-010-0122-1. [DOI] [PubMed] [Google Scholar]
  33. Xu J, Lombardi G, Jiao W, & Banfi G (2016). Effects of exercise on bone status in female subjects, from young girls to postmenopausal women: an overview of systematic reviews and meta-analyses. Sports Medicine, 46(8), 1165–1182. doi: 10.1007/s40279-016-0494-0. [DOI] [PubMed] [Google Scholar]
  34. Yin MT, & Brown TT (2016). HIV and Bone Complications: Understudied Populations and New Management Strategies. Current HIV/AIDS Reports, 13(6), 349–358. DOI: 10.1007/s11904-016-0341-9. [DOI] [PubMed] [Google Scholar]
  35. Yuan Y, Chen X, Zhang L, Wu J, Guo J, Zou D, … Zou J (2016). The roles of exercise in bone remodeling and in prevention and treatment of osteoporosis. Progress in Biophysics and Molecular Biology, 122(2), 122–130. doi: 10.1016/j.pbiomolbio.2015.11.005. [DOI] [PubMed] [Google Scholar]

RESOURCES