TABLE 1.
Summary of included studies.
| Author, years | Country | Selection criteria | Sex | Age | Number of participants | Intervention | Comparison | Primary Outcome(s) | Confirmation of fracture | Main results |
|---|---|---|---|---|---|---|---|---|---|---|
| Randomized controlled trial | ||||||||||
| McClung, 2001 [32] | International | At least one nonskeletal risk factor for HF, a T score < -4 at FN or a T score < -3 plus a hip-axis length of 11.1 cm or greater | W | >80 years | 3,886 | Risedronate 2.5 mg or 5 mg/d | Placebo | Incidence of HF | Radiography | RR = 0.8; 95%CI = 0.6–1.2; p = 0.35 |
| McCloskey, 2007 [33] | United Kingdom (community-dwelling) | Randomly recruited from general practice lists (not necessarily proven osteoporosis or any risk factors for fracture) | W | >75 years | 5,592 | Clodronate 800 mg/d | Placebo | Incidence of HF | Hospital notes, discharge/general practitioner letters, copies of radiographic reports, or review of radiographs | During the first year:HR = 1.31; 95%CI = 0.84-2.03During the third year: HR = 0.49; 95%CI = 0.23–1.06 |
| Greenspan, 2015 [34] | United states (nursing homes or assisted living facility) | T-score<-2 spine, hip or radius or history of VF or HF | W | >65 y | 181 | Single 5 mg dose of zoledronic acid | Placebo | Change in BMD of the total hip and spine at 12 months* | DXA* | OR = 0.76; 95%CI = 0.25–2.28; p = 0.62 |
| Costman, 2016 [35] | International | T score <-2.5 to -3.5 at the total hip or FN | W | >55 y | 2,240 | Romosozumab 210 mg/m | Placebo | Incidence of VF | Radiography | Data not shown concerning subjects >75 years |
| Post hoc analysis | ||||||||||
| Boonen, 2010 [36] | International | T-score < -2.5 at FN with or without VFx or T-score < -1.5 at FN with radiological evidence of at least two mild VFx or one moderate VF | ||||||||
| OR | ||||||||||
| 90 days after HF | M + W | >75years | 3,888 | Zoledronic acid 5 mg/y | Placebo | Incidence of clinical VF and nVF and any clinical fracture | Radiography | At 1 year: HR = 0.39; 95%CI 0.19–0.82; p = 0.09 | ||
| At 3 years: HR = 0.34; 95%CI = 0.21–0.55; P< 0.001 | ||||||||||
| Ensrud, 1997 [37] | United states | BMD at the FN of 0.68 g/cm2 or less (approximately Tscore < -2) and at least 1 VF | W | >75 years | 539 | Alendronate 5 mg/d then 10 mg/d | Placebo | Incidence of VF | Radiography | RR = 0.62; 95%CI = 0.41–0.94 |
| Boonen, 2004 [38] | International | T-score < -2.5 at FN or at least one VF | W | >80years | 1,392 | Risedronate 5 mg/d | Placebo | Incidence of VF | Radiography | After 1 year HR = 0.19; 95%CI = 0.09–0.40; P< 0.001After 3 years HR = 0.56; 95%CI = 0.39–0.81; P< 0.003 |
| Boonen, 2011 [39] | International | T score < −2.5 but > -4.0 at the lumbar spine or total hip | W | >75 years | 2,471 | Denosumab 60 mg/6m | Placebo | Incidence of VF and HF | Radiography | Significant reduction in the risk of HFx in subjects aged 75 years or older (2.3% placebo vs. 0.9% denosumab; p < 0.01) |
| Marcus, 2003 [40] | International | At least one moderate/two mild VFx or fewer than two moderate VFx and Tscore < -1 | W | >75years | 1,637 including 285 > 75years | Teriparatide 20 µg or 40 μg/d | Placebo | Relationship between risk of VF/nVF fractures and age | Radiography | Treatment was associated with a similar reduction in the relative risk of fracture in eachsubgroup of age |
| Nakano, 2013 [41] | Japan | Primary osteoporosis with one to five VF and T-score<-1.67 at the lumbar spine, FN, total hip, or distal radius | M + W | >75 y | 283 | Teriparatide 56.5µg/w | Placebo | Incidence of VF | Radiography | RR = 0.32; 95%CI = 0.13–0.80; p = 0.015 |
| McClung, 2012 [42] | International | T-score < -2.5 at either the lumbar spine or total hip and >-4.0 at both sites | W | >75 years | 2,471 | Denosumab 60mg/6 m | Placebo | Incidence of VF | Radiography | RR = 0.36, 95%CI = 0.25–0.53 |
| McClung, 2018 [43] | International | At least 2 mild or at least 1 moderate lumbar or thoracic VF or a history of nVF within the preceding 5 years with T-score<-2 at the lumbar spine or hip or without prior fracture but T-score<-3 | W | >80 y | 94 | Abaloparatide 80 μg/d | Placebo | Incidence of VF | Radiography | 2 new VFx in placebo group,0 new VFx in Abaloparatide group(not statistically significant) |
| Preplanned and post hoc analysis | ||||||||||
| Eastell, 2009 [44] | International | T-score<-2.5 at FN with or without evidence of existing VFx or a T-score<-1.5 at FN with radiological evidence of at least two mild VFx or one moderate VF | W | >75 y | 2,949 | Zoledronic acid 5 mg/y | Placebo | Incidence of VF, nVF and HF | Radiography | VF incidence (%): 4.8 (Zoledronate) vs 12 (Placebo); p < 0.0001 |
| HF incidence (%): 2.1 (Zoledronate) vs 2.7 (Placebo); p = 0.3511 | ||||||||||
| Prespecified subgroup analysis | ||||||||||
| Boonen, 2006 [45] | International | At least one moderate/two mild VFx or fewer than two moderate VFx and Tscore<-1 | W | >75 y | 244 | Teriparatide 20 μg/d | Placebo | Incidence of VF | Radiography | RR = 0.35; p < 0.05 |
| Costman, 2016 [46] | International | At least 2 mild or at least 1 moderate lumbar or thoracic vertebral fractures or a history of nonvertebral fracture within the preceding 5 years with T-score<-2 at the lumbar spine or hip or without prior fracture but T-score<-3 | W | >75 y | 248 | Abaloparatide 80 μg/d | Placebo | Incidence of VF | Radiography | RR = 0.48; 95%CI = 0.09–2.55 |
| Prospective cohort | ||||||||||
| Axelsson, 2017 [47] | Sweden | Prior HF | M + W | >80 years | 9,805 | Alendronate | No treatment | Incidence of HF | Code for surgical procedure | HR per year = 0.91; 95%CI = 0.85–0.97; P< 0.01 |
| Retrospective cohort | ||||||||||
| Bergman, 2018 [48] | Sweden | History of clinical fracture from 2006 to 2011 | M + W | >50 years | 83,104 including 22,830 > 80years | Alendronate, Risedronate, or Zoledronic acid | No treatment | Incidence of any clinical fracture and HF | ICD-10 codes | In adults over 80 years, during the first 6 months, the rate of HF was higher in bisphosphonate users than in non-users. From 6 to 12 months: the rate of HF was similar in users and non-users |
| Morin, 2007 [49] | Quebec | Hospitalization for HF between 1996 and 2002 | M + W | >65 y | 20,644 including 11,573 > 80 y | Etidronate, Alendronate, Risedronate, Raloxifene, Calcitonin or HRT | No treatment | Incidence of HF | ICD-9 codes | In adults over 80 years, HR = 0.92; 95%CI = 0.77–1.10 |
| Bawa, 2015 [50] | United states | Presence of a fragility fracture (wrist, proximal part of the humerus, hip, or vertebral) and prescription medication coverage as a part of insurance | M + W | >50 y | 7,502 (number of subjects >80 years not shown) | Bisphosphonates, Teriparatide, Denosumab, Raloxifene or Calcitonin | no treatment | Incidence of new HF, VF, Humerus or Wrist fracture | CPT codes | In adult over 80 years,VF:OR = 0.57; 95%CI = 0.42–0.78; p < 0.01HF: OR = 0.81; 95%CI = 0.61–1.07; p < 0.01 |
Abbreviations: HF = hip fracture; FN = femoral neck; cm = centimeter; W = women; y = years; mg = milligrams; d = days; RR = relative risk; CI = confidence interval; HR = hazard ratio; VF = Vertebral Fracture; BMD = bone mineral density; DXA = dual energy x‐ray absorptiometry; OR = odd radio; m = months; VFx = vertebral fractures; μg = microgram; M = men; w = weeks; nVF = nonvertebral Fracture; ICD = International Statistical Classification of Diseases; HRT = Hormone Replacement Therapy; CPT = Current Procedural Terminology.
∗ Secondary outcome : incidence of VF mesured by DXA.
In italic: studies included in meta analysis.