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Summary: In this study of 695 Australian older adults (aged >=50 years), we found that men and women had a similar trajectory of health-related quality of life (HRQoL) recovery following fragility fracture at any skeletal site. These results provide us with critical knowledge that improves our understanding of health outcomes post-fracture. Introduction: Mortality is higher in men than that in women following a fragility fracture, but it is unclear whether recovery of patient-reported outcomes such as health-related quality of life (HRQoL) differs between sexes. This study aimed to identify sex differences in HRQoL recovery 12 months post-fracture. Method(s): Data were from the Australian arm of the International Costs and Utilities Related to Osteoporotic Fractures Study (AusICUROS). Participants recruited to AusICUROS were adults aged >=50 years who sustained a fragility fracture. HRQoL was measured using the EQ-5D-3L at three time-points post-fracture: within 2 weeks (including pre-fracture recall) and at 4 and 12 months. Multivariate logistic regression analyses were undertaken, adjusting for confounders including age, education, income, and healthcare utilization post-fracture. Result(s): Overall, 695 AusICUROS participants (536 women, 77.1%) were eligible for analysis with fractures at the hip (n = 150), distal forearm (n = 261), vertebrae (n = 61), humerus (n = 52), and other skeletal sites (n = 171). At the time of fracture, men were younger, reported a higher income, and were more likely to be employed, compared with women. For all fracture sites combined, there were no differences between men and women in recovery to pre-fracture HRQoL at 12-month follow-up (adjusted OR = 1.09; 95% CI: 0.75-1.61). When stratified by fracture site, no significant sex differences were seen for hip (OR = 1.02; 95% CI: 0.42-2.52), distal forearm (OR = 1.60; 95% CI: 0.68-3.78), vertebral (OR = 2.28; 95% CI: 0.61-8.48), humeral (OR = 1.62; 95% CI: 0.16-9.99), and other fractures

BACKGROUND: Modelling and remodelling adapt bone morphology to accommodate strains commonly encountered during loading. If strains exceed a threshold threatening fracture, modelling-based bone formation increases bone volume reducing these strains. If unloading reduces strains below a threshold that inhibits resorption, increased remodelling-based bone resorption reduces bone volume restoring strains, but at the price of compromised bone volume and microstructure. As weight-bearing regions are adapted to greater strains, we hypothesized that microstructural deterioration will be more severe than at regions commonly adapted to low strains following spinal cord injury. METHODS: We quantified distal tibial, fibula and radius volumetric bone mineral density (vBMD) using high-resolution peripheral quantitative computed tomography in 31 men, mean age 43.5 years (range 23.5-75.0), 12 with tetraplegia and 19 with paraplegia of 0.7 to 18.6 years duration, and 102 healthy age- and sex-matched controls. Differences in morphology relative to controls were expressed as standardized deviation (SD) scores (mean ± SD). Standardized between-region differences in vBMD were expressed as SDs (95% confidence intervals, CI). RESULTS: Relative to controls, men with tetraplegia had deficits in total vBMD of -1.72 ± 1.38 SD at the distal tibia (p < 0.001) and - 0.68 ± 0.69 SD at distal fibula (p = 0.041), but not at the distal radius, despite paralysis. Deficits in men with paraplegia were -2.14 ± 1.50 SD (p < 0.001) at the distal tibia and -0.83 ± 0.98 SD (p = 0.005) at the distal fibula while distal radial total vBMD was 0.23 ± 1.02 (p = 0.371), not significantly increased, despite upper limb mobility. Comparing regions, in men with tetraplegia, distal tibial total vBMD was 1.04 SD (95%CI 0.07, 2.01) lower than at the distal fibula (p = 0.037) and 1.51 SD (95%CI 0.45, 2.57) lower than at the distal radius (p = 0.007); the latter two sites did not differ from each other. Results were simil

OBJECTIVE: To assess the antifracture efficacy and safety of a nutritional intervention in institutionalised older adults replete in vitamin D but with mean intakes of 600 mg/day calcium and <1 g/kg body weight protein/day. DESIGN: Two year cluster randomised controlled trial. SETTING: 60 accredited residential aged care facilities in Australia housing predominantly ambulant residents. PARTICIPANTS: 7195 permanent residents (4920 (68%) female; mean age 86.0 (SD 8.2) years). INTERVENTION: Facilities were stratified by location and organisation, with 30 facilities randomised to provide residents with additional milk, yoghurt, and cheese that contained 562 (166) mg/day calcium and 12 (6) g/day protein achieving a total intake of 1142 (353) mg calcium/day and 69 (15) g/day protein (1.1 g/kg body weight). The 30 control facilities maintained their usual menus, with residents consuming 700 (247) mg/day calcium and 58 (14) g/day protein (0.9 g/kg body weight). MAIN OUTCOME MEASURES: Group differences in incidence of fractures, falls, and all cause mortality. RESULTS: Data from 27 intervention facilities and 29 control facilities were analysed. A total of 324 fractures (135 hip fractures), 4302 falls, and 1974 deaths were observed. The intervention was associated with risk reductions of 33% for all fractures (121 v 203; hazard ratio 0.67, 95% confidence interval 0.48 to 0.93; P=0.02), 46% for hip fractures (42 v 93; 0.54, 0.35 to 0.83; P=0.005), and 11% for falls (1879 v 2423; 0.89, 0.78 to 0.98; P=0.04). The risk reduction for hip fractures and falls achieved significance at five months (P=0.02) and three months (P=0.004), respectively. Mortality was unchanged (900 v 1074; hazard ratio 1.01, 0.43 to 3.08). CONCLUSIONS: Improving calcium and protein intakes by using dairy foods is a readily accessible intervention that reduces the risk of falls and fractures commonly occurring in aged care residents. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN1

SUMMARY: Hypophosphatasia (HPP) is a rare and under-recognised genetic defect in bone mineralisation. Patients presenting with fragility fractures may be mistakenly diagnosed as having osteoporosis and prescribed antiresorptive therapy, a treatment which may increase fracture risk. Adult-onset HPPhypophosphatasia was identified in a 40-year-old woman who presented with bilateral atypical femoral fractures after 4 years of denosumab therapy. A low serum alkaline phosphatase (ALP) and increased serum vitamin B6 level signalled the diagnosis, which was later confirmed by identification of two recessive mutations of the ALPL gene. The patient was treated with teriparatide given the unavailability of ALP enzyme-replacement therapy (asfotase alfa). Fracture healing occurred, but impaired mobility persisted. HPP predisposes to atypical femoral fracture (AFF) during antiresorptive therapy; hence, bisphosphonates and denosumab are contraindicated in this condition. Screening patients with fracture or 'osteoporosis' to identify a low ALP level is recommended. LEARNING POINTS: Hypophosphatasia (HPP) is a rare and under-recognised cause of bone fragility produced by impaired matrix mineralisation that can be misdiagnosed as a fragility fracture due to age-related bone loss. Antiresorptive therapy is contraindicated in HPP. Low serum alkaline phosphatase (ALP) provides a clue to the diagnosis. Elevated serum vitamin B6 (an ALP substrate) is indicative of HPP, while identification of a mutation in the ALPL gene is confirmatory. Enzyme therapy with recombinant ALP (asfotase alfa) is currently prohibitively costly. Treatment with anabolic bone agents such as teriparatide has been reported, but whether normally mineralized bone is formed requires further study.

To determine whether stress fractures are associated with bone microstructural deterioration we quantified distal radial and the unfractured distal tibia using high resolution peripheral quantitative computed tomography in 26 cases with lower limb stress fractures (15 males, 11 females; mean age 37.1 ± 3.1 years) and 62 age-matched healthy controls (24 males, 38 females; mean age 35.0 ± 1.6 years). Relative to controls, in men, at the distal radius, cases had smaller cortical cross sectional area (CSA) (p = 0.012), higher porosity of the outer transitional zone (OTZ) (p = 0.006), inner transitional zone (ITZ) (p = 0.043) and the compact-appearing cortex (CC) (p = 0.023) while trabecular vBMD was lower (p = 0.002). At the distal tibia, cases also had a smaller cortical CSA (p = 0.008). Cortical porosity was not higher, but trabecular vBMD was lower (p = 0.001). Relative to controls, in women, cases had higher distal radial porosity of the OTZ (p = 0.028), ITZ (p = 0.030) not CC (p = 0.054). Trabecular vBMD was lower (p = 0.041). Distal tibial porosity was higher in the OTZ (p = 0.035), ITZ (p = 0.009), not CC. Stress fractures are associated with compromised cortical and trabecular microstructure.

INTRODUCTION: Measurement of bone mineral density (BMD) is recommended in patients with chronic kidney disease (CKD). However, most persons in the community and most patients with CKD have osteopenia, suggesting fracture risk is low. Bone loss compromises bone microarchitecture which increases fragility disproportionate to modest deficits in BMD. We therefore hypothesized that patients with CKD have reduced estimated failure load due to deterioration in microarchitecture irrespective of whether they have normal femoral neck (FN) BMD, osteopenia or osteoporosis. METHODS: We measured distal tibial and distal radial microarchitecture in 128 patients with CKD and 275 age- and sex-matched controls using high resolution peripheral quantitative computed tomography, FN-BMD using bone densitometry and estimated failure load at the distal appendicular sites using finite element analysis. RESULTS: Patients versus controls respectively had: lower tibial cortical area 219 (40.7) vs. 237 (35.3) mm2, p = 0.002, lower cortical volumetric BMD 543 (80.7) vs. 642 (81.7) mgHA/cm3 due to higher porosity 69.6 (6.19) vs. 61.9 (6.48)% and lower matrix mineral density 64.2 (0.62) vs. 65.1 (1.28)%, lower trabecular vBMD 92.2 (41.1) vs. 149 (43.0) mgHA/cm3 due to fewer and spatially disrupted trabeculae, lower FN-BMD 0.78 (0.12) vs. 0.94 (0.14) g/cm2 and reduced estimated failure load 3825 (1152) vs. 5778 (1467) N, all p < 0.001. Deterioration in microarchitecture and estimated failure load was most severe in patients and controls with osteoporosis. Patients with CKD with osteopenia and normal FN-BMD had more deteriorated tibial microarchitecture and estimated failure load than controls with BMD in the same category. In univariate analyses, microarchitecture and FN-BMD were both associated with estimated failure load. In multivariable analyses, only microarchitecture was independently associated with estimated failure load and accounted for 87% of the variance. CONCLUSIONS: Bone fragility is

To assess the antifracture efficacy and safety of a nutritional intervention in institutionalised older adults replete in vitamin D but with mean intakes of 600 mg/day calcium and <1 g/kg body weight protein/day. Two year cluster randomised controlled trial. 60 accredited residential aged care facilities in Australia housing predominantly ambulant residents. 7195 permanent residents (4920 (68%) female; mean age 86.0 (SD 8.2) years). Facilities were stratified by location and organisation, with 30 facilities randomised to provide residents with additional milk, yoghurt, and cheese that contained 562 (166) mg/day calcium and 12 (6) g/day protein achieving a total intake of 1142 (353) mg calcium/day and 69 (15) g/day protein (1.1 g/kg body weight). The 30 control facilities maintained their usual menus, with residents consuming 700 (247) mg/day calcium and 58 (14) g/day protein (0.9 g/kg body weight). Group differences in incidence of fractures, falls, and all cause mortality. Data from 27 intervention facilities and 29 control facilities were analysed. A total of 324 fractures (135 hip fractures), 4302 falls, and 1974 deaths were observed. The intervention was associated with risk reductions of 33% for all fractures (121v203; hazard ratio 0.67, 95% confidence interval 0.48 to 0.93; P=0.02), 46% for hip fractures (42v93; 0.54, 0.35 to 0.83; P=0.005), and 11% for falls (1879v2423; 0.89, 0.78 to 0.98; P=0.04). The risk reduction for hip fractures and falls achieved significance at five months (P=0.02) and three months (P=0.004), respectively. Mortality was unchanged (900v1074; hazard ratio 1.01, 0.43 to 3.08). Improving calcium and protein intakes by using dairy foods is a readily accessible intervention that reduces the risk of falls and fractures commonly occurring in aged care residents.