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Vitamin D supplementation is often used in the prevention and treatment of osteoporosis, but the role of vitamin D has lately been questioned. We aimed to investigate the effect of 3 months of daily vitamin D3 supplementation (70 µg [2800 IU] vs. placebo) initiated in winter months on bone health. This study is a double-blinded placebo-controlled randomized trial. Bone health was assessed by bone turnover markers, DXA, HRpQCT, and QCT scans. The participants were 81 healthy postmenopausal women with low 25(OH)D (< 50 nmol/l) and high PTH levels (> 6.9 pmol/l) at screening. Vitamin D3 supplementation significantly increased levels of 25(OH)D and 1,25(OH)2D by 59 nmol/l and 19 pmol/l, respectively, whereas PTH was reduced by 0.7 pmol/l (all p < 0.0001). Compared with placebo, vitamin D3 did not affect bone turnover markers, aBMD by DXA or trabecular bone score. Vitamin D3 increased trabecular vBMD (QCT scans) in the trochanter region (0.4 vs. − 0.7 g/cm3) and the femoral neck (2.1 vs. − 1.8 g/cm3) pall < 0.05. HRpQCT scans of the distal tibia showed reduced trabecular number (− 0.03 vs. 0.05 mm−1) and increased trabecular thickness (0.001 vs. − 0.005 mm), as well as an improved estimated bone strength as assessed by failure load (0.1 vs. − 0.1 kN), and stiffness (2.3 vs. − 3.1 kN/mm pall ≤ 0.01). Changes in 25(OH)D correlated significantly with changes in trabecular thickness, stiffness, and failure load. Three months of vitamin D3 supplementation improved bone strength and trabecular thickness in tibia, vBMD in the trochanter and femoral neck, but did not affect aBMD.

SummaryIt is not clear why type 2 diabetes (T2D) has an increased risk of fracture despite higher areal bone mineral density. This study showed that compared with controls, T2D patients had higher trabecular bone density but lower cortical bone density, resulting in a lower bone strength.IntroductionTo define the association between type 2 diabetes and bone architecture and measures of bone strength.MethodsThe study was part of the Vietnam Osteoporosis Study, in which 1115 women and 614 men aged ≥ 30 were randomly recruited from Ho Chi Minh City. HbA1c levels were measured with analyzers ADAMS™ A1c HA-8160 (Arkray, Kyoto, Japan). The diagnosis of T2D was made if HbA1c was ≥ 6.5%. Trabecular and cortical volumetric bone density (vBMD) was measured in the forearm and leg by a pQCT XCT2000 (Stratec, Germany). Polar stress strain index (pSSI) was derived from the pQCT measurements. Difference in bone parameters between T2D and non-diabetic individuals was assessed by the number of standard deviations (effect size [ES]) by the propensity score analysis.ResultsThe prevalence of T2D was ~ 8%. The results of propensity score matching for age, sex, and body mass index in 137 pairs of diabetic and non-diabetic individuals showed that T2D patients had significantly higher distal radius trabecular vBMD (ES 0.26; 95% CI, 0.02 to 0.50), but lower cortical vBMD (ES − 0.22; − 0.46 to 0.00) and reduced pSSI (ES − 0.23; − 0.47 to − 0.02) compared with non-diabetic individuals. Multiple linear regression analysis based on the entire sample confirmed the results of the propensity score analysis.ConclusionCompared with non-diabetic individuals, patients with T2D have greater trabecular but lower cortical vBMD which leads to lower bone strength.

SummaryMany female athletes are energy and/or estrogen deficient, but the independent effects on bone health have not been isolated. Energy deficiency was detrimental at the tibia while estrogen deficiency was detrimental at the radius. Nutrition must be considered alongside menstrual recovery when addressing compromised bone health in female athletes.IntroductionThe purpose of this study was to describe volumetric bone mineral density (vBMD), bone geometry, and estimated bone strength in exercising women (n = 60) grouped according to energy status (energy replete (EnR: n = 30) vs. energy deficient (EnD: n = 30)) and estrogen status (estrogen replete (E2R: n = 33) vs. estrogen deficient (E2D: n = 27)), resulting in four distinct groups: EnR + E2R (n = 17), EnR + E2D (n = 13), EnD + E2R (n = 16), EnD + E2D (n = 14).MethodsEnergy status was determined using the ratio of measured to predicted resting energy expenditure (mREE/pREE). Estrogen status was based on self-reported menstrual status confirmed by daily evaluation of urinary estrone-1-glucoronide (E1G), pregnanediol glucuronide (PdG), and luteinizing hormone (LH). Eumenorrheic women were considered E2R, amenorrheic women were E2D, and oligomenorrheic women were categorized based on history of menses in the past year. Bone was assessed using peripheral quantitative computed tomography (pQCT).ResultsEnD women exhibited lower total vBMD, trabecular vBMD, cortical area, and BSI at the distal tibia and lower total vBMD, smaller cortical area and cortical thickness, and larger endosteal circumference at the proximal tibia compared to EnR women (p < 0.042). E2D women had lower total and cortical vBMD, larger total and trabecular area, and lower BSI at the distal radius and lower cortical vBMD at the proximal radius compared to E2R women (p < 0.023). Energy and estrogen interacted to affect total and trabecular area at the distal tibia (p < 0.021).ConclusionsEfforts to correct energy deficiency, which in turn may promote reproductive health, are warranted in order to address the unique contributions of energy status versus estrogen status to bone health.

IntroductionSecond-generation high-resolution peripheral quantitative computed tomography (HR-pQCT) has provide higher quality of bone images with a voxel size of 61 µm, enabling direct measurements of trabecular thickness. In addition to the standard parameters, the non-metric trabecular parameters such as trabecular morphology (plate to rod-like structures), connectivity, and anisotropy can also be analyzed. The purpose of this study is to investigate deterioration of bone microstructure in healthy Japanese women by measuring standard and non-metric parameters using HR-pQCT.Materials and methodsStudy participants were 61 healthy Japanese women (31–70 years). The distal radius and tibia were scanned using second-generation HR-pQCT, and microstructures of trabecular and cortical bone were measured. Non-metric trabecular parameters included structure model index (SMI), trabecular bone pattern factor (TBPf), connectivity density (Conn.D), number of nodes (N.Nd/TV), degree of anisotropy (DA), and star volume of marrow space (V*ms). Estimated bone strength was evaluated by micro finite element analysis. Associations between bone microstructure, estimated bone strength, age, and menopause were analyzed.ResultsTrabecular number declined with age, and trabecular separation increased. SMI and TBPf increased, Conn.D and N.Nd/TV declined, and V*ms increased. Cortical BMD and thickness declined with age, and porosity increased. Stiffness and failure load decreased with age. Cortical thickness and estimated bone strength were affected by menopause. Cortical thickness was most associated with estimated bone strength.ConclusionsTrabecular and cortical bone microstructure were deteriorated markedly with age. Cortical thickness decreased after menopause and was most related to bone strength. Non-metric parameters give additional information about osteoporotic changes of trabecular bone.

Summary The association between lactation and bone size and strength was studied in 145 women 16 to 20 years after their last parturition. Longer cumulative duration of lactation was associated with larger bone size and strength later in life. Introduction Pregnancy and lactation have no permanent negative effect on maternal bone mineral density but may positively affect bone structure in the long term. We hypothesized that long lactation promotes periosteal bone apposition and hence increasing maternal bone strength. Methods Body composition, bone area, bone mineral content, and areal bone mineral density of whole body and left proximal femur were assessed using DXA, and cross-sectional area and volumetric bone mineral density of the left tibia shaft were measured by pQCT in 145 women (mean age 48 years, range 36–60 years) 16 to 20 years after their last parturition. Hip (HSI) and tibia strength indexes (TBSI) were calculated. Medical history and lifestyle factors including breastfeeding patterns and durations were collected via a self-administered questionnaire. Weight change during each pregnancy was collected from personal maternity tracking records. Results Sixteen to 20 years after the last parturition, women who had breastfed in total more than 33 months in their life, regardless of the number of children, had greater bone strength estimates of the hip (HSI = 1.92 vs. 1.61) and the tibia (TBSI = 5,507 vs. 4,705) owing to their greater bone size than mothers who had breastfed less than 12 months ( p  < 0.05 for all). The differences in bone strength estimates were independent of body height and weight, menopause status, use of hormone replacement therapy, and present leisure time physical activity level. Conclusion Breastfeeding is beneficial to maternal bone strength in the long run.

Abstract SummaryDecreased cortical bone density and bone strength at peak height velocity (PHV) were noted in girls with adolescent idiopathic scoliosis (AIS). These findings could provide the link to the previously reported observation that low bone mineral density (BMD) could contribute as one of the prognostic factors for curve progression that mostly occurs during PHV in AIS.IntroductionAs part of the studies related to aetiopathogenesis of AIS, we assessed bone qualities, bone mechanical strength and bone turnover markers (BTMs) focusing at the peri-pubertal period and PHV in AIS girls.Methods396 AIS girls in two separate cohorts were studied. Skeletal maturity was assessed using the validated thumb ossification composite index (TOCI). Bone qualities and strength were evaluated with high-resolution peripheral quantitative computed tomography (HR-pQCT) and finite element analysis (FEA).ResultsCohort-A included 179 girls (11.95 ± 0.95 years old). Girls at TOCI-4 had numerically the highest height velocity (0.71 ± 0.24 cm/month) corresponding to the PHV. Subjects at TOCI-4 had lower cortical volumetric BMD (672.36 ± 39.07 mg/mm3), cortical thickness (0.68 ± 0.08 mm) and apparent modulus (1601.54 ± 243.75 N/mm2) than: (a) those at TOCI-1–3 (724.99 ± 32.09 mg/mm3 (p < 0.001), 0.79 ± 0.11 mm (p < 0.001) and 1910.88 ± 374.75 N/mm2 (p < 0.001), respectively) and (b) those at TOCI-8 (732.28 ± 53.75 mg/mm3 (p < 0.001), 0.84 ± 0.14 mm (p < 0.001), 1889.11 ± 419.37 N/mm2 (p < 0.001), respectively). Cohort-B included 217 girls (12.22 ± 0.89 years old). Subjects at TOCI-4 had higher levels of C-terminal telopeptide of type 1 collagen (1524.70 ± 271.10 pg/L) and procollagen type 1 N-terminal propeptide (941.12 ± 161.39 µg/L) than those at TOCI-8 (845.71 ± 478.55 pg/L (p < 0.001) and 370.08 ± 197.04 µg/L (p < 0.001), respectively).ConclusionAIS girls had decreased cortical bone density and bone mechanical strength with elevated BTMs at PHV. Coupling of PHV with decreased cortical and FEA parameters could provide the link to the previously reported observation that low BMD could contribute as one of the prognostic factors for curve progression that mostly occurs during PHV in AIS.

IntroductionThe aim of this study was to compare bone mineral density (BMD) and geometric indices of hip bone strength in a group of obese sarcopenic premenopausal women (n = 27) and a group of obese premenopausal women with normal appendicular lean mass (ALM)/body mass index ratio (BMI) (n = 26).Materials and methodsThe ALM/BMI criterion of The Foundation for the National Institute of Health was used; women with an ALM/BMI ratio < 0.512 m2 were considered obese sarcopenic. Body composition and bone variables were measured by DXA. DXA measurements were completed for the whole body (WB), lumbar spine (L1–L4), total hip (TH) and femoral neck (FN). Hip geometry parameters including cross-sectional area (CSA), cross-sectional moment of inertia (CSMI), section modulus (Z), strength index (SI) and buckling ratio (BR) were derived by DXA.ResultsAge, weight and BMI were not significantly different between the two groups. Height, lean mass, skeletal muscle mass index, ALM and the ratio ALM/BMI were significantly higher in obese women with normal ALM/BMI ratio compared to obese sarcopenic women. Fat mass percentage was significantly higher in obese sarcopenic women compared to obese women with normal ALM/BMI ratio. WB BMC, TH BMD, FN BMD, CSA, CSMI and Z were significantly higher in obese women with normal ALM/BMI ratio compared to obese sarcopenic women. In the whole population (n = 53), ALM and the ratio ALM/BMI were positively correlated to WB BMC, CSA, CSMI and Z.ConclusionThe present study suggests that sarcopenia negatively influences bone mineral density and hip geometry parameters before menopause in eumenorrheic obese women.

SummaryBone health is assessed by bone mineral density (BMD). Other techniques such as trabecular bone score and microindentation could improve the risk of fracture’s estimation. Our chronic kidney disease (CKD) patients presented worse bone health (density, microarchitecture, mechanical properties) than controls. More than BMD should be done to evaluate patients at risk of fracture.IntroductionBMD measured by dual-energy X-ray absorptiometry (DXA) is used to assess bone health in end-stage renal disease (ESRD) patients. Recently, trabecular bone score (TBS) and microindentation that can measure microarchitectural and mechanical properties of bone have demonstrated better correlation with fractures than DXA in different populations. We aimed to characterize bone health (BMD, TBS, and strength) and calcium/phosphate metabolism in a cohort of 53 ESRD patients undergoing kidney transplantation (KT) and 94 controls with normal renal function.MethodsLaboratory workout, lumbar spine/hip BMD measurements (using DXA), lumbar spine TBS, and bone strength were carried out. The latter was assessed with an impact microindentation device, standardized as percentage of a reference value, and expressed as bone material strength index (BMSi) units. Multivariable linear regression was used to study differences between cases and controls adjusted by age, gender, and body mass index.ResultsAmong cases, serum calcium was 9.6 ± 0.7 mg/dl, phosphorus 4.4 ± 1.2 mg/dl, and intact parathyroid hormone 214 pg/ml [102–390]. Fourteen patients (26.4%) had prevalent asymptomatic fractures in spinal X-ray. BMD was significantly lower among ESRD patients compared to controls: lumbar 0.966 ± 0.15 vs 0.982 ± 0.15 (adjusted p = 0.037), total hip 0.852 ± 0.15 vs 0.902 ± 0.13 (adjusted p < 0.001), and femoral neck 0.733 ± 0.15 vs 0.775 ± 0.12 (adjusted p < 0.001), as were TBS (1.20 [1.11–1.30] vs 1.31 [1.19–1.43] (adjusted p < 0.001)) and BMSi (79 [71.8–84.2] vs 82. [77.5–88.9] (adjusted p = 0.005)).ConclusionsESRD patients undergoing transplant surgery have damaged bone health parameters (density, microarchitecture, and mechanical properties) despite acceptably controlled hyperparathyroidism. Detecting these abnormalities may assist in identifying patients at high risk of post-transplantation fractures.

SummaryWe compared the bone strength measured via quantitative computed tomography-based finite element method (QCT/FEM) between healthy adults with and without ossification of the posterior longitudinal ligament (OPLL). No statistically significant difference was observed in the bone strength between healthy adults with and without OPLL. Hyperostosis of the posterior longitudinal ligament in OPLL may not be associated with the systemic bone strength.IntroductionAlthough patients with OPLL have been reportedly associated with increased level of bone mineral density (BMD) using dual-energy X-ray absorptiometry (DXA), little is known about the bone strength in OPLL subjects. The aim of this study is to investigate the bone strength measured via QCT/FEM in healthy subjects with OPLL using the medical check-up data, including whole-body CT scans.MethodsWe examined 796 participants (529 men and 267 women) who underwent CT scans in a single health center between January 2008 and May 2009. We identified OPLL in whole spine and divided the subjects into two groups: non-OPLL and OPLL groups. We calculated the predicted bone strength (PBS) of the proximal femur using QCT/FEM and examined the bone mineral status of the calcaneus using quantitative ultrasound (QUS). We compared the PBS and the QUS parameters between the non-OPLL and OPLL groups.ResultsSeventy-four subjects (9.3%; 57 men and 17 women) were diagnosed with OPLL in the whole spine. The OPLL group was significantly older than the non-OPLL group. No statistically significant difference was observed in the PBS and the QUS parameters between the non-OPLL and OPLL groups in both sexes. Furthermore, no statistically significant difference was noted in the PBS and the QUS parameters between two groups in age- and gender-matched analysis.ConclusionsOur results suggest that hyperostosis of the posterior longitudinal ligament in OPLL may not be associated with bone strength and bone mineral status at the extremities.

Summary Wnt signaling and its bone tissue–specific inhibitor sclerostin are key regulators of bone homeostasis. The therapeutic potential of anti-sclerostin antibodies (Scl-Abs), for bone mass recovery and fragility fracture prevention in low bone mass phenotypes, has been supported by animal studies. The Scl-Ab romosozumab is currently used for osteoporosis treatment. Introduction Wnt signaling is a key regulator of skeletal development and homeostasis; germinal mutations affecting genes encoding components, inhibitors, and enhancers of the Wnt pathways were shown to be responsible for the development of rare congenital metabolic bone disorders. Sclerostin is a bone tissue–specific inhibitor of the Wnt/β-catenin pathway, secreted by osteocytes, negatively regulating osteogenic differentiation and bone formation, and promoting osteoclastogenesis and bone resorption. Purpose and methods Here, we reviewed current knowledge on the role of sclerostin and Wnt pathways in bone metabolism and skeletal disorders, and on the state of the art of therapy with sclerostin-neutralizing antibodies in low-bone-mass diseases. Results Various in vivo studies on animal models of human low-bone-mass diseases showed that targeting sclerostin to recover bone mass, restore bone strength, and prevent fragility fracture was safe and effective in osteoporosis, osteogenesis imperfecta, and osteoporosis pseudoglioma. Currently, only treatment with romosozumab, a humanized monoclonal anti-sclerostin antibody, has been approved in human clinical practice for the treatment of osteoporosis, showing a valuable capability to increase BMD at various skeletal sites and reduce the occurrence of new vertebral, non-vertebral, and hip fragility fractures in treated male and female osteoporotic patients. Conclusions Preclinical studies demonstrated safety and efficacy of therapy with anti-sclerostin monoclonal antibodies in the preservation/restoration of bone mass and prevention of fragility fractures in low-bone-mass clinical phenotypes, other than osteoporosis, to be validated by clinical studies for their approved translation into prevalent clinical practice.