The Effect of Fall Biomechanics on Risk for Hip Fracture in Older Adults: A Cohort Study of Video-Captured Falls in Long-Term Care

Over 95% of hip fractures in older adults are caused by falls, yet only 1% to 2% of falls result in hip fracture. Our current understanding of the types of falls that lead to hip fracture is based on reports by the faller or witness. We analyzed videos of real-life falls in long-term care to provide objective evidence on the factors that separate falls that result in hip fracture from falls that do not. Between 2007 and 2018, we video-captured 2377 falls by 646 residents in two long-term care facilities. Hip fracture was documented in 30 falls. We analyzed each video with a structured questionnaire, and used generalized estimating equations (GEEs) to determine relative risk ratios (RRs) for hip fracture associated with various fall characteristics. All hip fractures involved falls from standing height, and pelvis impact with the ground. After excluding falls from lower than standing height, risk for hip fracture was higher for sideways landing configurations (RR = 5.50; 95% CI, 2.36–12.78) than forward or backward, and for falls causing hip impact (3.38; 95% CI, 1.49–7.67). However, hip fracture risk was just as high in falls initially directed sideways as forward (1.14; 95% CI, 0.49–2.67), due to the tendency for rotation during descent. Falling while using a mobility aid was associated with lower fracture risk (0.30; 95% CI, 0.09–1.00). Seventy percent of hip fractures involved impact to the posterolateral aspect of the pelvis. Hip protectors were worn in 73% of falls, and hip fracture risk was lower in falls where hip protectors were worn (0.45; 95% CI, 0.21–0.99). Age and sex were not associated with fracture risk. There was no evidence of spontaneous fractures. In this first study of video-captured falls causing hip fracture, we show that the biomechanics of falls involving hip fracture were different than nonfracture falls for fall height, fall direction, impact locations, and use of hip protectors. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.     

Effect of compliant flooring on impact force during falls on the hip.

Compliant flooring represents a promising but understudied strategy for reducing impact force and hip fracture risk due to falls in high-risk environments such as nursing homes, hospitals, gymnasiums, and senior centers. We conducted "pelvis release experiments" with young women (n=15) to determine whether floor stiffness influences peak hip impact force during safe, low-height falls. During the trials, we used a pelvic sling and electromagnet to lift and instantly release the participant from a height of 5 cm above a force plate, which measured the force applied to the hip region during impact. Trials were conducted for rigid floor conditions and with layers of ethylene vinyl acetate foam rubber overlying the floor that we regarded as firm (1.5-cm thick; stiffness=263 kN/m), semifirm (4.5-cm thick; stiffness=95 kN/m), semisoft (7.5-cm thick; stiffness=67 kN/m), and soft (10.5-cm thick; stiffness=59 kN/m). When compared to the rigid condition, peak hip impact force averaged 8% lower in the firm condition and 15% lower in the semifirm condition. Peak forces were not significantly different between the semifirm, semisoft, and soft floor conditions, indicating that a 4.5 cm-thick foam mat provides nearly the same force attenuation as a 10.5 cm-thick mat. These results support the need for laboratory experiments to measure the effect of floor stiffness on postural stability and for clinical trials to determine the effect of compliant flooring on hip fracture incidence in high-risk environments.     

Assessment of Bone Fragility in Patients With Multiple Myeloma Using QCT‐Based Finite Element Modeling

Multiple myeloma (MM) is a malignant plasma cell disease associated with severe bone destruction. Surgical intervention is often required to prevent vertebral body collapse and resulting neurological complications; however, its necessity is determined by measuring lesion size or number, without considering bone biomechanics. Finite element (FE) modeling, which simulates the physiological loading, may improve the prediction of fragility. To test this, we developed a quantitative computed tomography (QCT)‐based FE model of the vertebra and applied it to a dataset of MM patients with and without prevalent fracture. FE models were generated from vertebral QCT scans of the T₁₂ (T₁₁ if T₁₂ was fractured) of 104 MM patients, 45 with fracture and 59 without, using a low‐dose scan protocol (1.5 mm slice thickness, 4.0 to 6.5 mSv effective dose). A calibration phantom enabled the conversion of the CT Hounsfield units to FE material properties. Compressive loading of the vertebral body was simulated and the stiffness, yield load, and work to yield determined. To compare the parameters between fracture and nonfracture groups, t tests were used, and standardized odds ratios (sOR, normalized to standard deviation) and 95% confidence intervals were calculated. FE parameters were compared to mineral and structural parameters using linear regression. Patients with fracture showed lower vertebral stiffness (–15.2%; p = 0.010; sOR = 1.73; 95% CI, 1.11 to 2.70), yield force (–21.5%; p = 0.002; sOR = 2.09; 95% CI, 1.27 to 3.43), and work to yield (–27.4%; p = 0.001; sOR = 2.28; 95% CI, 1.33 to 3.92) compared to nonfracture patients. All parameters correlated significantly with vBMD (stiffness: R² = 0.57, yield force: R² = 0.59, work to yield: R² = 0.50, p < 0.001), BV/TV (stiffness: R² = 0.56, yield force: R² = 0.58, work to yield: R² = 0.49, p < 0.001), and Tb.Sp (stiffness: R² = 0.51, yield force: R² = 0.53, work to yield: R² = 0.45, p < 0.001). FE modeling identified MM patients with compromised mechanical integrity of the vertebra. Higher sOR values were obtained for the biomechanical compared to structural or mineral measures, suggesting that FE modeling improves fragility assessment in these patients. © 2016 American Society for Bone and Mineral Research.     

Higher-Impact Physical Activity Is Associated With Maintenance of Bone Mineral Density But Not Reduced Incident Falls or Fractures in Older Men: The Concord Health and Aging in Men Project

High-impact physical activities with bone strains of high magnitude and frequency may benefit bone health. This study aimed to investigate the longitudinal associations between changes in loading intensities and application rates, estimated from self-reported physical activity, with bone mineral density (BMD) changes over 5 years and also with incident falls over 2 years and long-term incident fractures in community-dwelling older men. A total of 1599 men (mean age 76.8 ± 5.4 years) from the Concord Health and Aging in Men Project (CHAMP) were assessed at baseline (2005–2007) and at 2- and 5-year follow-up. At each time point, hip and lumbar spine BMD were measured by dual-energy X-ray absorptiometry, and physical activity energy expenditure over the past week was self-reported via the Physical Activity Scale for the Elderly (PASE) questionnaire. Sum effective load ratings (ELRs) and peak force were estimated from the PASE questionnaire, reflecting the total and highest loading intensity and application rate of physical activities, respectively. Participants were contacted every 4 months over 2 years to self-report falls and over 6.0 ± 2.2 years for fractures. Hip fractures were ascertained by data linkage for 8.9 ± 3.6 years. Compared with sum ELR and PASE scores, peak force demonstrated the greatest standardized effect size for BMD maintenance at the spine (β = 9.77 mg/cm²), total hip (β = 14.14 mg/cm²), and femoral neck (β = 13.72 mg/cm²) after adjustment for covariates, including PASE components (all p < .01). Only PASE scores were significantly associated with reduced falls risk (standardized incident rate ratio = 0.90, 95% confidence interval 0.81–1.00, p = .04). All physical activity measures were significantly associated with reduced incident fractures in univariate analyses, but none remained significant after multivariable adjustments. Older men who engaged in physical activity of high and rapid impact maintained higher BMD, while higher energy expenditure was associated with reduced falls risk. Coupling traditional physical activity data with bone loading estimates may improve understanding of the relationships between physical activity and bone health. © 2020 American Society for Bone and Mineral Research (ASBMR).     

A Pooled Analysis of Fall Incidence From Placebo-Controlled Trials of Denosumab

Recent studies suggest that the RANK/RANKL system impacts muscle function and/or mass. In the pivotal placebo-controlled fracture trial of the RANKL inhibitor denosumab in women with postmenopausal osteoporosis, treatment was associated with a lower incidence of non-fracture-related falls (p = 0.02). This ad hoc exploratory analysis pooled data from five placebo-controlled trials of denosumab to determine consistency across trials, if any, of the reduction of fall incidence. The analysis included trials in women with postmenopausal osteoporosis and low bone mass, men with osteoporosis, women receiving adjuvant aromatase inhibitors for breast cancer, and men receiving androgen deprivation therapy for prostate cancer. The analysis was stratified by trial, and only included data from the placebo-controlled period of each trial. A time-to-event analysis of first fall and exposure-adjusted subject incidence rates of falls were analyzed. Falls were reported and captured as adverse events. The analysis comprised 10,036 individuals; 5030 received denosumab 60 mg subcutaneously once every 6 months for 12 to 36 months and 5006 received placebo. Kaplan–Meier estimates showed an occurrence of falls in 6.5% of subjects in the placebo group compared with 5.2% of subjects in the denosumab group (hazard ratio = 0.79; 95% confidence interval 0.66–0.93; p = 0.0061). Heterogeneity in study designs did not permit overall assessment of association with fracture outcomes. In conclusion, denosumab may reduce the risk of falls in addition to its established fracture risk reduction by reducing bone resorption and increasing bone mass. These observations require further exploration and confirmation in studies with muscle function or falls as the primary outcome. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research..     

Early Changes in Bone Density,Microarchitecture, Bone Resorption,and Inflammation Predict the Clinical Outcome 12 Weeks After Conservatively Treated Distal Radius Fractures: An Exploratory Study

Fracture healing is an active process with early changes in bone and inflammation. We performed an exploratory study evaluating the association between early changes in densitometric, structural, biomechanical, and biochemical bone parameters during the first weeks of fracture healing and wrist‐specific pain and disability at 12 weeks in postmenopausal women with a conservatively treated distal radius fracture. Eighteen patients (aged 64 ± 8 years) were evaluated at 1 to 2 and 3 to 4 weeks postfracture, using high‐resolution peripheral quantitative computed tomography (HR‐pQCT), micro‐finite element analysis, serum procollagen type‐I N‐terminal propeptide (P1NP), carboxy‐terminal telopeptide of type I collagen (ICTP), and high‐sensitive C‐reactive protein (hsCRP). After 12 weeks, patients rated their pain and disability using Patient Rated Wrist Evaluation (PRWE) questionnaire. Additionally, Quick Disability of the Arm Shoulder and Hand (QuickDASH) questionnaire and active wrist range of motion was evaluated. Linear regression models were used to study the relationship between changes in bone parameters and in hsCRP from visit 1 to 2 and PRWE score after 12 weeks. A lower PRWE outcome, indicating better outcome, was significantly related to an early increase in trabecular bone mineral density (BMD) (β ?0.96 [95% CI ?1.75 to ?0.16], R² = 0.37), in torsional stiffness (?0.14 [?0.28 to ?0.004], R² = 0.31), and to an early decrease in trabecular separation (209 [15 to 402], R² = 0.33) and in ICTP (12.1 [0.0 to 24.1], R² = 0.34). Similar results were found for QuickDASH. Higher total dorsal and palmar flexion range of motion was significantly related to early increase in hsCRP (9.62 [3.90 to 15.34], R² = 0.52). This exploratory study indicates that the assessment of early changes in trabecular BMD, trabecular separation, calculated torsional stiffness, bone resorption marker ICTP, and hsCRP after a distal radius fracture provides valuable information regarding the 12‐week clinical outcome in terms of pain, disability, and range of motion and validates its use in studies on the process of early fracture healing. © 2014 American Society for Bone and Mineral Research.     

Predictive Value of DXA Appendicular Lean Mass for Incident Fractures,Falls, and Mortality,Independent of Prior Falls,FRAX, and BMD: Findings from the Women's Health Initiative (WHI)

In the Women's Health Initiative (WHI), we investigated associations between baseline dual-energy X-ray absorptiometry (DXA) appendicular lean mass (ALM) and risk of incident fractures, falls, and mortality (separately for each outcome) among older postmenopausal women, accounting for bone mineral density (BMD), prior falls, and Fracture Risk Assessment Tool (FRAX^®) probability. The WHI is a prospective study of postmenopausal women undertaken at 40 US sites. We used an extension of Poisson regression to investigate the relationship between baseline ALM (corrected for height²) and incident fracture outcomes, presented here for major osteoporotic fracture (MOF: hip, clinical vertebral, forearm, or proximal humerus), falls, and death. Associations were adjusted for age, time since baseline and randomization group, or additionally for femoral neck (FN) BMD, prior falls, or FRAX probability (MOF without BMD) and are reported as gradient of risk (GR: hazard ratio for first incident fracture per SD increment) in ALM/height² (GR). Data were available for 11,187 women (mean [SD] age 63.3 [7.4] years). In the base models (adjusted for age, follow-up time, and randomization group), greater ALM/height² was associated with lower risk of incident MOF (GR = 0.88; 95% confidence interval [CI] 0.83–0.94). The association was independent of prior falls but was attenuated by FRAX probability. Adjustment for FN BMD T-score led to attenuation and inversion of the risk relationship (GR = 1.06; 95% CI 0.98–1.14). There were no associations between ALM/height² and incident falls. However, there was a 7% to 15% increase in risk of death during follow-up for each SD greater ALM/height², depending on specific adjustment. In WHI, and consistent with our findings in older men (Osteoporotic Fractures in Men [MrOS] study cohorts), the predictive value of DXA-ALM for future clinical fracture is attenuated (and potentially inverted) after adjustment for femoral neck BMD T-score. However, intriguing positive, but modest, associations between ALM/height² and mortality remain robust. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).     

Surface stiffness affects impact force during a fall on the outstretched hand

Falls on the outstretched hand are among the most common causes of traumatic bone fracture. However, little is known regarding the biomechanical factors that affect the risk for injury during these events. In the present study, we explored how upper-extremity impact forces during forward falls are affected by modification of surface stiffness, an intervention applicable to high-risk environments such as nursing homes, playgrounds, and gymnasiums. Results from both experimental and linear biomechanical models suggest that during a fall onto an infinitely stiff surface, hand contact force is governed by a high-frequency transient (having an associated peak force F_max1), followed by a low-frequency oscillation (having an associated lower magnitude peak force F_max2). Practical decreases in surface stiffness attenuate F_max1 but not F_max2 or the magnitude of force transmitted to the shoulder. Model simulations reveal that this arises from the compliant surface's ability to decrease the velocity across the wrist damping elements at the moment of impact (which governs F_max1) but inability to substantially reduce the peak deflection of the shoulder spring (which governs F_max2). Comparison between model predictions and previous data on fracture force suggests that feasible compliant surface designs may prevent wrist injuries during falls from standing height or lower, because F_max1 will be attenuated and F_max2 will remain below injurious levels. However, such surfaces cannot prevent F_max2 from exceeding injurious levels during falls from greater heights and therefore likely provide little protection against upper-extremity injuries in these cases.     

Force attenuation in trochanteric soft tissues during impact from a fall

The risk for hip fracture from a fall is known to decrease with increased body mass index (weight/height²), a relative measure of obesity. To explore whether this reduced risk is due to the protective effect of increased soft-tissue cushioning in obese individuals, we used an impact pendulum and surrogate human pelvis to conduct simulated fall impact experiments on trochanteric soft tissues harvested from the cadavers of nine elderly individuals. For each impact, the total applied energy was 140 J. Peak forces ranged from 4,050 to 6,420 N, and tissue energy absorption ranged from 8.4 to 81.6 J. Increased tissue thickness correlated strongly with both decreased peak force (r² = 0.91) and increased tissue energy absorption (r² = 0.76). However, peak forces in all cases were within 1 SD of previously reported average fracture forces forces elderly cadaveric femora. This suggests that force attenuation in trochanteric soft tissues alone is insufficient to prevent hip fracture in falls in which an elderly person lands directly on the hip. In such falls, additional energy-absorbing mechanisms, such as breaking the fall with an outstretched hand and eccentric contraction of the quadriceps during descent, are likely to be involved if fracture does not occur.     

Effects of loading rate on strength of the proximal femur

Results from previous quasi-static mechanical tests indicate that femurs from elderly subjects fail in vitro at forces 50% below those available in a fall from standing height. However, bone is a rate-dependent material, and it is not known whether this imbalance is present at rates of loading which occur in a fall. Based on recent data on time to peak force and body positions at impact during simulated falls, we designed a high rate test of the femur in a loading configuration meant to represent a fall on the hip. We used elderly (mean age 73.5±7.4 (SD) years) and younger adult (32.7±12.8 years) cadaveric femurs to investigate whether (1) the strength, stiffness, and energy absorption capacity of the femur increases under high rate loading conditions; (2) elderly femurs have reduced strength, stiffness, and energy absorption capacity compared with younger adult femurs at this loading rate; and (3) densitometric and geometric measures taken at the hip correlate with the measured fracture loads. Femurs were scanned using dual-energy X-ray absorptiometry (DXA) and then tested to failure in a fall loading configuration at a displacement rate of 100 mm/second. The fracture load in elderly and younger adult femurs increased by about 20% with a 50-fold increase in displacement rate. However, energy absorption did not increase with displacement rate because of a twofold increase in stiffness at the higher loading rate. Age-related differences in strength and energy absorption capacity were consistent with those found previously for a displacement rate of 2 mm/second. There were moderate to strong correlations between fracture load and DXA variables, with the best correlation provided by cross-sectional area (r²=0.77) and bone mineral density (BMD) (r²=0.72) at the femoral neck. Our results indicate that, even at rates of loading applied during a fall, the estimated impact force in a fall on the hip is 35% greater than the average fracture load of the elderly femur. Moreover, the relationship we found between femoral neck BMD and fracture load indicates that an increase in femoral neck BMD of more than 20% would be required to raise the strength of the femur to the level of the impact load. As clinical trials of pharmacologic interventions have demonstrated increases in BMD of only a few percent at best, our results emphasize the continuing need for intervention strategies that focus on fall prevention and on reducing the severity of those falls that do occur.     

Changes in in vivo knee loading with a variable‐stiffness intervention shoe correlate with changes in the knee adduction moment

External knee adduction moment can be reduced using footwear interventions, but the exact changes in in vivo medial joint loading remain unknown. An instrumented knee replacement was used to assess changes in in vivo medial joint loading in a single patient walking with a variable‐stiffness intervention shoe. We hypothesized that during walking with a load modifying variable‐stiffness shoe intervention: (1) the first peak knee adduction moment will be reduced compared to a subject's personal shoes; (2) the first peak in vivo medial contact force will be reduced compared to personal shoes; and (3) the reduction in knee adduction moment will be correlated with the reduction in medial contact force. The instrumentation included a motion capture system, force plate, and the instrumented knee prosthesis. The intervention shoe reduced the first peak knee adduction moment (13.3%, p = 0.011) and medial compartment joint contact force (12.3%; p = 0.008) compared to the personal shoe. The change in first peak knee adduction moment was significantly correlated with the change in first peak medial contact force (R² = 0.67, p = 0.007). Thus, for a single subject with a total knee prosthesis the variable‐stiffness shoe reduces loading on the affected compartment of the joint. The reductions in the external knee adduction moment are indicative of reductions in in vivo medial compressive force with this intervention. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:1548–1553, 2010     

The heterogeneity in femoral neck structure and strength

Most measures of femoral neck strength derived using dual‐energy X‐ray absorptiometry or computed tomography (CT) assume the femoral neck is a cylinder with a single cortical thickness. We hypothesized that these simplifications introduce errors in estimating strength and that detailed analyses will identify new parameters that more accurately predict femoral neck strength. High‐resolution CT data were used to evaluate 457 cross‐sectional slices along the femoral neck of 12 postmortem specimens. Cortical morphology was measured in each cross‐section. The distribution of cortical thicknesses was evaluated to determine whether the mean or median better estimated central tendency. Finite‐element models were used to calculate the stresses in each cross‐section resulting from the peak hip joint forces created during a sideways fall. The relationship between cortical morphology and peak bone stress along the femoral neck was analyzed using multivariate regression analysis. In all cross‐sections, cortical thicknesses were non‐normally distributed and skewed toward smaller thicknesses (p < 0.0001). The central tendency of cortical thickness was best estimated by the median, not the mean. Stress increased as the median cortical thickness decreased along the femoral neck. The median, not mean, cortical thickness combined with anterior‐posterior diameter best predicted peak bone stress generated during a sideways fall (R² = 0.66, p < 0.001). Heterogeneity in the structure of the femoral neck determines the diversity of its strength. The median cortical thickness best predicted peak femoral neck stress and is likely to be a relevant predictor of femoral neck fragility. © 2013 American Society for Bone and Mineral Research.     

Risk factors for hip impact during real-life falls captured on video in long-term care

Summary

Hip fracture risk is increased by landing on the hip. We examined factors that contribute to hip impact during real-life falls in long-term care facilities. Our results indicate that hip impact is equally likely in falls initially directed forward as sideways and more common among individuals with dependent Activities of Daily Living (ADL) performance.

Introduction

The risk for hip fracture in older adults increases 30-fold by impacting the hip during a fall. This study examined biomechanical and health status factors that contribute to hip impact through the analysis of real-life falls captured on video in long-term care (LTC) facilities.

Methods

Over a 7-year period, we captured 520 falls experienced by 160 residents who provided consent for releasing their health records. Each video was analyzed by a three-member team using a validated questionnaire to determine whether impact occurred to the hip or hand, the initial fall direction and landing configuration, attempts of stepping responses, and use of mobility aids. We also collected information related to resident physical and cognitive function, disease diagnoses, and use of medications from the Minimum Data Set.

Results

Hip impact occurred in 40 % of falls. Falling forward or sideways was significantly associated with higher odds of hip impact, compared to falling backward (OR 4.2, 95 % CI 2.4–7.1) and straight down (7.9, 4.1–15.6). In 32 % of sideways falls, individuals rotated to land backward. This substantially reduced the odds for hip impact (0.1, 0.03–0.4). Tendency for body rotation was decreased for individuals with dependent ADL performance (0.43, 0.2–1.0).

Conclusions

Hip impact was equally likely in falls initially directed forward as sideways, due to the tendency for axial body rotation during descent. A rotation from sideways to backward decreased the odds of hip impact 10-fold. Our results may contribute to improvements in risk assessment and strategies to reduce risk for hip fracture in older adults.

     

Identifying Novel Clinical Surrogates to Assess Human Bone Fracture Toughness

Fracture risk does not solely depend on strength but also on fracture toughness; ie, the ability of bone material to resist crack initiation and propagation. Because resistance to crack growth largely depends on bone properties at the tissue level, including collagen characteristics, current X‐ray based assessment tools may not be suitable to identify age‐related, disease‐related, or treatment‐related changes in fracture toughness. To identify useful clinical surrogates that could improve the assessment of fracture resistance, we investigated the potential of ¹H nuclear magnetic resonance spectroscopy (NMR) and reference point indentation (RPI) to explain age‐related variance in fracture toughness. Harvested from cadaveric femurs (62 human donors), single‐edge notched beam (SENB) specimens of cortical bone underwent fracture toughness testing (R‐curve method). NMR‐derived bound water showed the strongest correlation with fracture toughness properties (r = 0.63 for crack initiation, r = 0.35 for crack growth, and r = 0.45 for overall fracture toughness; p < 0.01). Multivariate analyses indicated that the age‐related decrease in different fracture toughness properties were best explained by a combination of NMR properties including pore water and RPI‐derived tissue stiffness with age as a significant covariate (adjusted R² = 53.3%, 23.9%, and 35.2% for crack initiation, crack growth, and overall toughness, respectively; p < 0.001). These findings reflect the existence of many contributors to fracture toughness and emphasize the utility of a multimodal assessment of fracture resistance. Exploring the mechanistic origin of fracture toughness, glycation‐mediated nonenzymatic collagen crosslinks and intracortical porosity are possible determinants of bone fracture toughness and could explain the sensitivity of NMR to changes in fracture toughness. Assuming fracture toughness is clinically important to the ability of bone to resist fracture, our results suggest that improvements in fracture risk assessment could potentially be achieved by accounting for water distribution (quantitative ultrashort echo time magnetic resonance imaging) and by a local measure of tissue resistance to indentation, RPI. © 2015 American Society for Bone and Mineral Research.     

Are the High Hip Fracture Rates Among Norwegian Women Explained by Impaired Bone Material Properties?

Hip fracture rates in Norway rank among the highest in the world, more than double that of Spanish women. Previous studies were unable to demonstrate significant differences between the two populations with respect to bone mass or calcium metabolism. In order to test whether the difference in fracture propensity between both populations could be explained by differences in bone material quality we assessed bone material strength using microindentation in 42 Norwegian and 46 Spanish women with normal BMD values, without clinical or morphometric vertebral fractures, no clinical or laboratory signs of secondary osteoporosis, and without use of drugs with known influence on bone metabolism. Bone material properties were assessed by microindentation of the thick cortex of the mid tibia following local anesthesia of the area using the Osteoprobe device (Active Life Scientific, Santa Barbara, CA, USA). Indentation distance was standardized against a calibration phantom of methylmethacrylate and results, as percentage of this reference value, expressed as bone material strength index units (BMSi). We found that the bone material properties reflected in the BMSi value of Norwegian women was significantly inferior when compared to Spanish women (77 ± 7.1 versus 80.7 ± 7.8, p < 0.001). Total hip BMD was significantly higher in Norwegian women (1.218 g/cm² versus 0.938 g/cm², p < 0.001) but regression analysis revealed that indentation values did not vary with BMD r² = 0.03 or age r² = 0.04. In conclusion Norwegian women show impaired bone material properties, higher bone mass, and were taller than Spanish women. The increased height will increase the impact on bone after falls, and impaired bone material properties may further enhance the risk fracture after such falls. These ethnic differences in bone material properties may partly explain the higher propensity for fracture in Norwegian women. © 2015 American Society for Bone and Mineral Research.     

Use of selective serotonin reuptake inhibitors and risk of fracture: a systematic review and meta-analysis

Previous studies have reported inconsistent findings regarding the association between the use of selective serotonin reuptake inhibitors (SSRIs) and the risk of fracture. We identified relevant studies by searching three electronic databases (MEDLINE, EMBASE, and the Cochrane Library) from their inception to October 20, 2010. Two evaluators independently extracted data. Because of heterogeneity, we used random‐effects meta‐analysis to obtain pooled estimates of effect. We identified 12 studies: seven case‐control studies and five cohort studies. A meta‐analysis of these 12 observational studies showed that the overall risk of fracture was higher among people using SSRIs (adjusted odds ratio [OR] = 1.69, 95% confidence interval [CI] 1.51–1.90, I² = 89.9%). Subgroup analysis by adjusted number of key risk factors for osteoporotic fracture showed a greater increased fracture risk in those adjusted for fewer than four variables (adjusted OR = 1.83, 95% CI 1.57–2.13, I² = 88.0%) than those adjusted for four or more variables (adjusted OR = 1.38, 95% CI 1.27–1.49, I² = 46.1%). The pooled ORs anatomical site of fracture in the hip/femur, spine, and wrist/forearm were 2.06 (95% CI 1.84–2.30, I² = 62.3%), 1.34 (95% CI 1.13–1.59, I² = 48.5%), and 1.51 (95% CI 1.26–1.82, I² = 76.6%), respectively. Subgroup analysis by exposure duration revealed that the strength of the association decreased with a longer window of SSRI administration before the index date. The risk of fracture was greater within 6 weeks before the index date (adjusted OR = 3.83, 95% CI 1.96–7.49, I² = 41.5%) than 6 weeks or more (adjusted OR = 1.60, 95% CI 0.93–2.76, I² = 63.1%). Fracture risk associated with SSRI use may have a significant clinical impact. Clinicians should carefully consider bone mineral density screening before prescribing SSRIs and proper management for high‐risk populations. © 2012 American Society for Bone and Mineral Research.     

A Polygenic Risk Score as a Risk Factor for Medication-Associated Fractures

Some commonly prescribed drugs are associated with increased risk of osteoporotic fractures. However, fracture risk stratification using skeletal measures is not often performed to identify those at risk before these medications are prescribed. We tested whether a genomically predicted skeletal measure, speed of sound (gSOS) from heel ultrasound, which was developed in 341,449 individuals from UK Biobank and tested in a separate subset consisting of 80,027 individuals, is an independent risk factor for fracture in users of fracture-related drugs (FRDs). To do this, we first assessed 80,014 UK Biobank participants (including 12,678 FRD users) for incident major osteoporotic fracture (MOF, n = 1189) and incident hip fracture (n = 209). Effects of gSOS on incident fracture were adjusted for baseline clinical fracture risk factors. We found that each standard deviation decrease in gSOS increased the adjusted odds of MOF by 42% (95% confidence interval [CI] 1.34–1.51, p < 2 × 10⁻¹⁶) and of hip fracture by 31% (95% CI 1.15–1.50, p = 9 × 10⁻⁵). gSOS below versus above the mean increased the adjusted odds of MOF by 79% (95% CI 1.58–2.01, p < 2 × 10⁻¹⁶) and of hip fracture by 42% (95% CI 1.08–1.88, p = 1.3 × 10⁻²). Among FRD users, each standard deviation decrease in gSOS increased the adjusted odds of MOF by 29% (n_MOF = 256, 95% CI 1.14–1.46, p = 7 × 10⁻⁵) and of hip fracture by 30% (n_{hip fracture} = 68, 95% CI 1.02–1.65, p = 0.0335). FRD users with gSOS below versus above the mean had a 54% increased adjusted odds of MOF (95% 1.19–1.99, p = 8.95 × 10⁻⁴) and a twofold increased adjusted odds of hip fracture (95% 1.19–3.31, p = 8.5 × 10⁻³). We therefore showed that genomically predicted heel SOS is independently associated with incident fracture among FRD users. © 2020 American Society for Bone and Mineral Research.     

The Effect of a Screening and Treatment Program for the Prevention of Fractures in Older Women: A Randomized Pragmatic Trial

Population screening for fracture risk may reduce the fracture incidence. In this randomized pragmatic trial, the SALT Osteoporosis Study (SOS), we studied whether screening for fracture risk and subsequent treatment in primary care can reduce fractures compared with usual care. A total of 11,032 women aged 65 to 90 years with ≥1 clinical risk factor for fractures were individually randomized to screening (n = 5575) or usual care (n = 5457). Participants in the screening group underwent a screening program, including bone densitometry and vertebral fracture assessment. Participants with a high 10-year fracture probability (FRAX) or a vertebral fracture were offered treatment with anti-osteoporosis medication by their general practitioner. Incident fractures as reported by questionnaires were verified with medical records. Follow-up was completed by 94% of the participants (mean follow-up = 3.7 years). Of the 5575 participants in the screening group, 1417 (25.4%) had an indication for anti-osteoporosis medication. Screening and subsequent treatment had no statistically significant effect on the primary outcome fracture (hazard ratio [HR] = 0.97; 95% confidence interval [CI] 0.87–1.08), nor on the secondary outcomes osteoporotic fractures (HR = 0.91; 95% CI 0.81–1.03), major osteoporotic fractures (HR = 0.91; 95% CI 0.80–1.04), hip fractures (HR = 0.91; 95% CI 0.71–1.15), falls (odds ratio [OR] = 0.91; 95% CI 0.72–1.15), or mortality (HR = 1.03; 95% CI 0.91–1.17). Post hoc explorative finding suggested that screening might be most effective after a recent fracture (HR = 0.65; 95% CI 0.44–0.96 for major osteoporotic fractures and HR = 0.38; 95% CI 0.18–0.79 for hip fractures). The results of this study might have been compromised by nonparticipation and medication nonadherence in the screening group. Overall, this study does not provide sufficient indications to consider screening for fracture prevention. However, we cannot exclude its clinical relevance to reduce (major) osteoporotic fractures and hip fractures because of the relatively small number of women with a treatment indication in the intervention group. © 2019 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc.     

Long‐Term Proton Pump Inhibitor Therapy and Falls and Fractures in Elderly Women: A Prospective Cohort Study

Proton pump inhibitors (PPIs) are widely used in the elderly. Recent studies have suggested that long‐term PPI therapy is associated with fractures in the elderly, however the mechanism remains unknown. We investigated the association between long‐term PPI therapy ≥1 year and fracture risk factors including bone structure, falls, and balance‐related function in a post hoc analysis of a longitudinal population‐based prospective cohort of elderly postmenopausal women and replicated the findings in a second prospective study of falling in elderly postmenopausal women. Long‐term PPI therapy was associated with increased risk of falls and fracture‐related hospitalizations; adjusted odds ratio (AOR) 2.17; 95% CI, 1.25–3.77; p = 0.006 and 1.95; 95% CI, 1.20–3.16; p = 0.007, respectively. In the replication study, long‐term PPI use was associated with an increased risk of self‐reported falling; AOR, 1.51; 95% CI, 1.00–2.27; p = 0.049. No association of long‐term PPI therapy with bone structure was observed; however, questionnaire‐assessed falls‐associated metrics such as limiting outdoor activity (p = 0.002) and indoor activity (p = 0.001) due to fear of falling, dizziness (p < 0.001) and numbness of feet (p = 0.017) and objective clinical measurement such as Timed Up and Go (p = 0.002) and Romberg eyes closed (p = 0.025) tests were all significantly impaired in long‐term PPI users. Long‐term PPI users were also more likely to have low vitamin B12 levels than non‐users (50% versus 21%, p = 0.003). In conclusion, similar to previous studies, we identified an increased fracture risk in subjects on long‐term PPI therapy. This increase in fracture risk in elderly women, already at high risk of fracture, appears to be mediated via increased falls risk and falling rather than impaired bone structure and should be carefully considered when prescribing long‐term PPI therapy. © 2014 American Society for Bone and Mineral Research.     

Prediction of fracture risk in men: a cohort study

FRAX is a tool that identifies individuals with high fracture risk who will benefit from pharmacological treatment of osteoporosis. However, a majority of fractures among elderly occur in people without osteoporosis and most occur after a fall. Our aim was to accurately identify men with a high future risk of fracture, independent of cause. In the population‐based Uppsala Longitudinal Study of Adult Men (ULSAM) and using survival analysis we studied different models' prognostic values (R²) for any fracture and hip fracture within 10 years from age 50 (n = 2322), 60 (n = 1852), 71 (n = 1221), and 82 (n = 526) years. During the total follow‐up period from age 50 years, 897 fractures occurred in 585 individuals. Of these, 281 were hip fractures occurring in 189 individuals. The rates of any fracture were 5.7/1000 person‐years at risk from age 50 years and 25.9/1000 person‐years at risk from age 82 years. Corresponding hip fractures rates were 2.9 and 11.7/1000 person‐years at risk. The FRAX model included all variables in FRAX except bone mineral density. The full model combining FRAX variables, comorbidity, medications, and behavioral factors explained 25% to 45% of all fractures and 80% to 92% of hip fractures, depending on age. The corresponding prognostic values of the FRAX model were 7% to 17% for all fractures and 41% to 60% for hip fractures. Net reclassification improvement (NRI) comparing the full model with the FRAX model ranged between 40% and 53% for any fracture and between 40% and 87% for hip fracture. Within the highest quintile of predicted fracture risk with the full model, one‐third of the men will have a fracture within 10 years after age 71 years and two‐thirds after age 82 years. We conclude that the addition of comorbidity, medication, and behavioral factors to the clinical components of FRAX can substantially improve the ability to identify men at high risk of fracture, especially hip fracture. © 2012 American Society for Bone and Mineral Research.