Hip fracture reduction as an endpoint in osteoporosis guidelines: methodological concerns raised by the Japan GL 2025.

Meta-analyses conducted >15 years ago reported that improvements in bone mineral density (BMD) were associated with reduction in vertebral and nonvertebral fractures in osteoporosis trials. Numerous studies have been conducted since then, incorporating new therapies with different mechanisms of action and enrolling many more subjects. To extend these prior analyses, we conducted a meta-regression of 38 placebo-controlled trials of 19 therapeutic agents to determine the association between improvements in BMD and reductions in fracture risk. We used a linear model to examine the relationship between mean percent difference in BMD change between treatment and placebo groups and the logarithm of the relative risk. We found that greater improvements in BMD were strongly associated with greater reductions in vertebral and hip fractures but not nonvertebral fractures. For vertebral fracture, the r2 values for total hip, femoral neck, and lumbar spine BMD change were 0.56, 0.54, and 0.63, respectively (p ≤ 0.0002). For a 2% or 6% improvement in total hip BMD, we might expect a 28% or 66% reduction, respectively, in vertebral fracture risk. For hip fracture, the r2 values for total hip, femoral neck, and lumbar spine BMD change were 0.48 (p = 0.01), 0.42 (p = 0.02), and 0.22 (ns), respectively. For a 2% or 6% improvement in total hip BMD, we might expect a 16% or 40% reduction in hip fracture risk. In conclusion, our results extend prior observations that larger improvements in dual-energy X-ray absorptiometry (DXA)-based BMD are associated with greater reductions in fracture risk, particularly for vertebral and hip fractures. Although these results cannot be directly applied to predict the treatment benefit in an individual patient, they provide compelling evidence that improvements in BMD with osteoporosis therapies may be useful surrogate endpoints for fracture in trials of new therapeutic agents. © 2019 American Society for Bone and Mineral Research.

Overdiagnosis and Overtreatment of Osteoporosis: A Wolf in Sheep's Clothing.

BackgroundElderly nursing home residents are at increased risk of hip fracture; however, the efficacy of fracture prevention strategies in this population is unclear.ObjectiveWe performed a scoping review of randomized controlled trials of interventions tested in the long-term care (LTC) setting, examining hip fracture outcomes.MethodsWe searched for citations in 6 respective electronic searches, supplemented by hand searches. Two reviewers independently reviewed all citations and full-text papers; consensus was achieved on final inclusion. Data was abstracted in duplicate.FindingsWe reviewed 22,349 abstracts or citations and 949 full-text papers. Data from 20 trials were included: 7 - vitamin D (n = 12,875 participants), 2 - sunlight exposure (n = 522), 1 - alendronate (n = 327), 1 - fluoride (n = 460), 4 – exercise or multimodal interventions (n = 8,165), and 5 - hip protectors (n = 2,594). Vitamin D, particularly vitamin D3 ≥800 IU orally daily, reduced hip fracture risk. Hip protectors reduced hip fractures in included studies, although a recent large study not meeting inclusion criteria was negative. Fluoride and sunlight exposure did not significantly reduce hip fractures. Falls were reduced in three studies of exercise or multimodal interventions, with one study suggesting reduced hip fractures in a secondary analysis. A staff education and risk assessment strategy did not significantly reduce falls or hip fractures. In a study underpowered for fracture outcomes, alendronate did not significantly reduce hip fractures in LTC.ConclusionsThe intervention with the strongest evidence for reduction of hip fractures in LTC is Vitamin D supplementation; more research on other interventions is needed.

Estrogen treatment does not reduce fractures?

Efficacy and safety of pharmacological agents in managing osteoporosis in the old old: Review of the evidence

To assess whether hip protectors used among women living in the community in the United Kingdom and at high risk of hip fracture, lead to a reduction in hip fracture. Pragmatic randomized controlled trial (RCT). Primary care with participants being recruited largely from general practitioners' patient lists. Women aged 70 years and over with one or more risk factors for hip fracture (i.e., low body weight, current smoker, a prior fracture, family history of hip fracture). Three pairs of hip protectors of the "shell" type mailed to participants with instructions on how to use them. Reduction in hip fractures. 1,388 and 2,781 women aged 70 years or over were randomized to be given three pairs of hip protectors or act as controls, respectively. We followed up both groups of women for a minimum of 24 months (maximum 42 months, median 28). Compliance was poor with only 31% of participants reporting that they wore the hip protectors on a daily basis at 12 months. Intention-to-treat analysis showed that there was no statistically significant difference in the unadjusted odds ratios (ORs) of sustaining a hip fracture between the groups (OR = 1.19; 95% confidence interval, 0.80 to 1.78, p = 0.40). Adjustment for important covariates did not materially change these findings (OR = 1.17; 95% CI, 0.78 to 1.75). Comparing the rate of hip fracture between those women who regularly wore the devices and the control group yielded an OR of 1.12 (95% CI, 0.58 to 2.03; p = 0.83). This study is the largest RCT of hip protectors to date and provides no evidence of an effect of hip protectors among women living independently and at high risk of fracture.

Background In Sweden 70,000 people suffer fragility fractures annually, including 16,000 hip fractures with one-year mortality of up to 25%. Strategies to prevent falls, improve physical function, and enhance bone strength have shown mixed results. Aim To evaluate the incidence of hip and other fragility fractures following a fracture prevention intervention and assess baseline risk factors for long-term fracture outcomes. Methods 1,233 rural Swedish women aged 70–100 years in 2002 were followed until 2021 after a primary care-based, non-randomized graded fracture prevention intervention 2002–2004 that included physical activity, fall prevention, and pharmacological treatment tailored to hip fracture risk. Fractures were identified through radiology reports 2002–2021. Results The most common fractures occurred in the hip with 236 women sustaining 268 hip fractures with highest incidence in women aged 90–94 years. One-year hip fracture mortality was 27%. Hip fractures occurred in 17.7% of the intervention group (77/434) and 19.9% of controls (159/799, p = 0.36). Repeated fragility fractures occurred in 14.1% of the intervention group and 18.6% of controls (OR 0.71; 95% CI 0.53–1.0, p = 0.047), particularly when one fracture involved the hip (OR 0.54 (95% CI 0.31–0.95), p = 0.037). Increasing age (HR 1.8–4.0), height >167 cm (HR 1.6; 95% CI 1.1–2.2), and weight <60 kg (HR 1.5; 95% CI 1.1–2.0) were significant baseline risk factors. Conclusions We noticed a non-significant reduction in hip fractures after 20 years, yet repeated fractures were less frequent in the intervention group suggesting a potential long-term benefit. Older, taller and lighter women were at greater risk for hip fracture.

Background To inform recommendations by the Canadian Task Force on Preventive Health Care, we reviewed evidence on the benefits, harms, and acceptability of screening and treatment, and on the accuracy of risk prediction tools for the primary prevention of fragility fractures among adults aged 40 years and older in primary care. Methods For screening effectiveness, accuracy of risk prediction tools, and treatment benefits, our search methods involved integrating studies published up to 2016 from an existing systematic review. Then, to locate more recent studies and any evidence relating to acceptability and treatment harms, we searched online databases

Osteoporosis and osteopenia are associated with increased fracture incidence in postmenopausal women. We aimed to determine the comparative effectiveness of various available pharmacological therapies. We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, ISI Web of Science, and Scopus for randomized controlled trials that enrolled postmenopausal women with primary osteoporosis and evaluated the risk of hip, vertebral, or nonvertebral fractures. A network meta-analysis was conducted using the multivariate random effects method. We included 107 trials (193,987 postmenopausal women; mean age, 66 years; 55% white; median follow-up, 28 months). A significant reduction in hip fractures was observed with romosozumab, alendronate, zoledronate, risedronate, denosumab, estrogen with progesterone, and calcium in combination with vitamin D. A significant reduction in nonvertebral fractures was observed with abaloparatide, romosozumab, denosumab, teriparatide, alendronate, risedronate, zoledronate, lasofoxifene, tibolone, estrogen with progesterone, and vitamin D. A significant reduction in vertebral fractures was observed with abaloparatide, teriparatide, parathyroid hormone 1-84, romosozumab, strontium ranelate, denosumab, zoledronate, risedronate, alendronate, ibandronate, raloxifene, bazedoxifene, lasofoxifene, estrogen with progesterone, tibolone, and calcitonin. Teriparatide, abaloparatide, denosumab, and romosozumab were associated with the highest relative risk reductions, whereas ibandronate and selective estrogen receptor modulators had lower efficacy. The evidence for the treatment of fractures with vitamin D and calcium remains limited despite numerous large trials. This network meta-analysis provides comparative effective estimates for the various available treatments to reduce the risk of fragility fractures in postmenopausal women.

Hip fractures are an important cause of morbidity and mortality in the elderly. Hip protectors are padded undergarments designed to decrease the impact of a fall on the hip. We systematically reviewed randomized controlled trials of hip protectors to determine if they reduce hip fractures in the elderly. Analyses were pooled according to participant residence--community or institutional (the latter, included nursing homes, residential group homes or seniors' hostels). We included individually randomized and statistically adjusted cluster randomized trials. Seven trials of 12- to 28-month duration were included. The Safehip brand of hip protector was used in most studies. Compliance rates in the treatment groups varied from 31 to 68%. In four trials including a total of 5,696 community-dwelling seniors, the hip fracture rates in control groups ranged from 1.1 to 7.4%, and the pooled risk difference with hip protector allocation was 0% [95% confidence intervals (CI), -1%, +1%), with a relative risk of 1.07 (0.81, 1.42). In three trials including 1,188 institutionalized elderly participants, hip fracture rates in the control groups varied from 8 to 19.4%, and the pooled risk difference for sustaining one or more hip fractures with hip protector allocation was -3.7% (95% CI, -7.4%, 0.1%), with a relative risk of 0.56 (0.31, 1.01) (with statistically significant heterogeneity of treatment effect). In a post-hoc subgroup analysis of two trials comprised of exclusively nursing home residents, the risk difference with hip protector allocation was -4.4% (-8.09, -0.76) with a relative risk of 0.50 (0.28, 0.91) (n=1,014). Thus, there is little evidence to support the use of hip protectors outside the nursing home setting. The potential benefit of hip protectors in reducing hip fractures in nursing home residents requires further confirmation.

Physical activity has been related to enhanced bone mass and improved physical functioning and thus may reduce the risk for osteoporotic fracture. To determine whether higher levels of physical activity are related to lower incidence of hip, wrist, and vertebral fractures. Prospective cohort study. Four clinical centers in Baltimore, Maryland; Portland, Oregon; Minneapolis, Minnesota; and the Monongahela Valley, Pennsylvania. 9704 nonblack women 65 years of age or older. Physical activity was assessed by questionnaire at baseline. Hip and wrist fractures were followed for an average of 7.6 years. The incidence of vertebral fracture was determined morphometrically by using radiography at baseline and an average of 3.7 years later. Higher levels of leisure time, sport activity, and household chores and fewer hours of sitting daily were associated with a significantly reduced relative risk for hip fracture after adjustment for age, dietary factors, falls at baseline, and functional and health status. Very active women (fourth and fifth quintiles) had a statistically significant 36% reduction in hip fractures (relative risk, 0.64 [95% CI, 0.45 to 0.891) compared with the least active women (lowest quintile). The intensity of physical activity was also related to fracture risk: Moderately to vigorously active women had statistically significant reductions of 42% and 33% in risk for hip and vertebral fractures, respectively, compared with inactive women. Total physical activity, hours of household chores per day, and hours of sitting per day were not significantly associated with wrist or vertebral fractures. Among older community-dwelling women, physical activity is associated with a reduced risk for hip fracture but not wrist or vertebral fracture.

It is easy to believe the assertion by Drs. Hussain and Barer that some patients with Alzheimer's disease are malnourished and that nutrition may be neglected in the rehabilitation of those who experience hip fractures. However, they offer no evidence to support the broad claim that “greater attention to nutritional problems in Alzheimer's patients may go further to decrease the risk of hip fracture than external hip protector pads.” Indeed, the role of nutrition in the pathogenesis of hip fractures is quite controversial. Ecological analyses reveal an inverse relationship between hip fracture rates and per capita consumption of protein and calcium,1 whereas population-based studies show inconsistent and generally small effects. Higher calcium intake, for example, has been associated with a reduced risk of hip fracture,2, 3 an increased risk,4, 5 or no effect at all.6, 7 Recently, a randomized controlled trial demonstrated a 17% reduction in nonspine fractures, and a 23% reduction in hip fractures, with vitamin D and calcium supplementation over 3 years in a nursing home population in France,8 where foods are not fortified with vitamin D. These results could not be confirmed in a similar trial in the Netherlands, however.9 Our group is not involved in the development or testing of energy-absorbing hip pads. We mentioned this approach to prophylaxis because of our observation that, of all possible kinds of fractures, only the risk of hip fractures was substantially increased among patients with Alzheimer's disease.10 Thus, an intervention aimed solely at hip fracture prophylaxis would likely be effective in this group. Studies have shown that hip fractures result from falls on the hip when kinetic energy is high and bone density in the proximal femur is low and when protective soft tissues are reduced.11 The importance of the latter finding was borne out in a trial by Lauritzen and colleagues in a Danish nursing home population, where the use of energy-absorbing hip pads reduced the risk of hip fracture by more than half.12 Consequently, this would appear to be a promising approach to hip fracture prevention, especially since the demented patients who fracture are those who are most mobile13 and presumably the best nourished. L. Joseph Melton III, MD Mayo Clinic Rochester, MN

ABSTRACTThe Screening for Osteoporosis in Older Women for the Prevention of Fracture (SCOOP) study was a community‐based screening intervention in women aged 70 to 85 years in the United Kingdom. In the screening arm, licensed osteoporosis treatments were recommended in women identified to be at high risk of hip fracture using the FRAX risk assessment tool (including bone mineral density measurement). In the control arm, standard care was provided. Screening led to a 28% reduction in hip fractures over 5 years. In this planned post hoc analysis, we wished to examine for interactions between screening effectiveness on fracture outcome (any, osteoporotic, and hip fractures) on the one hand and baseline FRAX 10‐year probability of hip fracture on the other. All analyses were conducted on an intention‐to‐treat basis, based on the group to which women were randomized, irrespective of whether screening was completed. Of 12,483 eligible participants, 6233 women were randomized to screening, with treatment recommended in 898 (14.4%). No evidence of an effect or interaction was observed for the outcomes of any fracture or osteoporotic fracture. In the screening arm, 54 fewer hip fractures were observed than in the control arm (164 versus 218, 2.6% versus 3.5%), and commensurate with treatment being targeted to those at highest hip fracture risk, the effect on hip fracture increased with baseline FRAX hip fracture probability (p = 0.021 for interaction); for example, at the 10th percentile of baseline FRAX hip probability (2.6%), there was no evidence that hip fractures were reduced (hazard ratio [HR] = 0.93; 95% confidence interval [CI] 0.71 to 1.23), but at the 90th percentile (16.6%), there was a 33% reduction (HR = 0.67; 95% CI 0.53 to 0.84). Prior fracture and parental history of hip fracture positively influenced screening effectiveness on hip fracture risk. We conclude that women at high risk of hip fracture based on FRAX probability are responsive to appropriate osteoporosis management. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc.

Is Evidence-Based Medicine Evidence Based?

The effect of vitamin D supplementation on skeletal, vascular, or cancer outcomes: a trial sequential meta-analysis