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High-resolution peripheral quantitative computed tomography (HR-pQCT) captures novel aspects of bone geometry, volumetric bone mineral density and offers the ability to measure bone microarchitecture, but data relating measures obtained from this technique to diabetic status are inconsistent in women and lacking in men. Here, we report an analysis from the Hertfordshire Cohort Study, where we were able to study associations between bone microarchitecture from HR-pQCT of distal radius and distal tibia in 332 participants (177 men and 155 women) aged 72.1–81.4 years with or without diabetes mellitus (DM); n  = 29 (18 men and 11 women) and n  = 303, respectively. Statistical analyses were performed separately for women and men. The mean (SD) age of participants was 76.4 (2.6) and 76.1 (2.5) years in women and men, respectively. Participants with DM differed significantly in terms of weight in both women (70.4 ± 12.3 vs. 80.3 ± 18.3 kg; p  = 0.015) and men (81.7 ± 11.4 vs. 92.8 ± 16.3 kg; p  < 0.001) but no differences were found in height, smoking status, alcohol intake, social class and physical activity among women or men. Analyses in women revealed that cortical pore volume (Ct.Po.V) was higher in participants with DM and close to statistical significance for cortical porosity (Ct.Po) ( β  = 0.76 [0.12, 1.41] z -score, p  = 0.020 and β  = 0.62 [−0.02, 1.27] z -score, p  = 0.059, respectively) at the distal radius. Adjustment for weight did not materially affect the relationship described for Ct.Po.V ( β  = 0.74 [0.09, 1.39], p  = 0.027) and Ct.Po ( β  = 0.65 [−0.01, 1.30], p  = 0.053) at the distal radius. After adjustment for weight, analyses in men revealed that Ct.Po and Ct.Po.V were higher in participants with DM ( β  = 0.57 [0.09, 1.06] z -score, p  = 0.021 and β  = 0.48 [0.01, 0.95] z -score, p  = 0.044, respectively) at the distal tibia. Analyses of distal radial and tibial trabecular bone parameters according to diabetic status revealed no significant differences among men or women after adjustment for weight. We found higher cortical porosity and cortical pore volume at the distal tibia in men with DM and higher cortical pore volume at the distal radius in women with a non-significant tendency for higher cortical porosity. The results of our study suggest that deficits in cortical bone exist both in older men and women with DM.

Parathyroid hormone increases both bone formation and bone resorption, and combining it with an antiresorptive agent might enhance its effects on bone mineral density. Eighty-three men, 46 to 85 years of age, with low bone mineral density were randomly assigned to receive alendronate, parathyroid hormone, or both; alendronate therapy was given for 30 months, and parathyroid hormone therapy was begun at month 6. Bone mineral density at the lumbar spine and the femoral neck increased significantly more with parathyroid hormone alone than with alendronate alone or combination therapy. Alendronate may attenuate PTH-induced bone formation. Osteoporosis affects more than 20 million people in the United States and leads to about 1.5 million fractures in this country each year. 1 Although osteoporotic fractures are more common in women, about 30 percent of such fractures occur in men. 2 Alendronate, a potent nitrogen-containing bisphosphonate, inhibits osteoclastic bone resorption. 3 Alendronate increases bone mineral density and reduces the risk of fracture in women 4 – 6 and men 7 , 8 with osteoporosis. Once-daily administration of a parathyroid hormone fragment also increases bone mineral density in men with osteoporosis 9 , 10 and in estrogen-deficient women 11 – 13 and reduces the risk of fracture in postmenopausal women with . . .

Summary Strontium ranelate appears to influence more than alendronate distal tibia bone microstructure as assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT), and biomechanically relevant parameters as assessed by micro-finite element analysis (μFEA), over 2 years, in postmenopausal osteoporotic women. Introduction Bone microstructure changes are a target in osteoporosis treatment to increase bone strength and reduce fracture risk. Methods Using HR-pQCT, we investigated the effects on distal tibia and radius microstructure of strontium ranelate (SrRan; 2 g/day) or alendronate (70 mg/week) for 2 years in postmenopausal osteoporotic women. This exploratory randomized, double-blind trial evaluated HR-pQCT and FEA parameters, areal bone mineral density (BMD), and bone turnover markers. Results In the intention-to-treat population ( n  = 83, age: 64 ± 8 years; lumbar T-score: −2.8 ± 0.8 [DXA]), distal tibia Cortical Thickness (CTh) and Density (DCort), and cancellous BV/TV increased by 6.3%, 1.4%, and 2.5%, respectively (all P  < 0.005), with SrRan, but not with alendronate (0.9%, 0.4%, and 0.8%, NS) ( P  < 0.05 for all above between-group differences). Difference for CTh evaluated with a distance transformation method was close to significance ( P  = 0.06). The estimated failure load increased with SrRan (+2.1%, P  < 0.005), not with alendronate (−0.6%, NS) (between-group difference, P  < 0.01). Cortical stress was lower with SrRan ( P  < 0.05); both treatments decreased trabecular stress. At distal radius, there was no between-group difference other than DCort ( P  < 0.05). Bone turnover markers decreased with alendronate; bALP increased (+21%) and serum-CTX-I decreased (−1%) after 2 years of SrRan (between-group difference at each time point for both markers, P  < 0.0001). Both treatments were well tolerated. Conclusions Within the constraints of HR-pQCT method, and while a possible artefactual contribution of strontium cannot be quantified, SrRan appeared to influence distal tibia bone microstructure and FEA-determined biomechanical parameters more than alendronate. However, the magnitude of the differences is unclear and requires confirmation with another method.

Background Treatment of segmental bone loss remains a major challenge in orthopaedic surgery. Traditional techniques (eg, autograft) and newer techniques (eg, recombinant human bone morphogenetic protein-2 [rhBMP-2]) have well-established performance limitations and safety concerns respectively. Consequently there is an unmet need for osteoinductive bone graft substitutes that may eliminate or reduce the use of rhBMP-2. Questions/purposes Using an established rabbit radius osteotomy defect model with positive (autogenous bone graft) and negative (empty sham) control groups, we asked: (1) whether a collagen-glycosaminoglycan scaffold alone can heal the defect, (2) whether the addition of hydroxyapatite particles to the collagen scaffold promote faster healing, and (3) whether the collagen-glycosaminoglycan and collagen-hydroxyapatite scaffolds are able to promote faster healing (by carrying a low dose rhBMP-2). Methods A 15-mm transosseous radius defect in 4-month-old skeletally mature New Zealand White rabbits were treated with either collagen-hydroxyapatite or collagen-glycosaminoglycan scaffolds with and without rhBMP-2. Autogenous bone graft served as a positive control. Time-series radiographs at four intervals and postmortem micro-CT and histological analysis at 16 weeks were performed. Qualitative histological analysis of postmortem explants, and qualitative and volumetric 3-D analysis of standard radiographs and micro-CT scans enabled direct comparison of healing between test groups. Results Six weeks after implantation the collagen-glycosaminoglycan group had callus occupying greater than ½ the defect, whereas the sham (empty) control defect was still empty and the autogenous bone graft defect was completely filled with unremodeled bone. At 6 weeks, the collagen-hydroxyapatite scaffold groups showed greater defect filling with dense callus compared with the collagen-glycosaminoglycan controls. At 16 weeks, the autogenous bone graft groups showed evidence of early-stage medullary canal formation beginning at the proximal and distal defect borders. The collagen-glycosaminoglycan and collagen-glycosaminoglycan-rhBMP-2 groups had nearly complete medullary canal formation and anatomic healing at 16 weeks. However, collagen-hydroxyapatite-rhBMP-2 scaffolds showed the best levels of healing, exhibiting a dense callus which completely filled the defect. Conclusions The collagen-hydroxyapatite scaffold showed comparable healing to the current gold standard of autogenous bone graft. It also performed comparably to collagen-glycosaminoglycan-rhBMP-2, a representative commercial device in current clinical use, but without the cost and safety concerns. Clinical Relevance The collagen-glycosaminoglycan scaffold may be suitable for a low load-bearing defect. The collagen-hydroxyapatite scaffold may be suitable for a load-bearing defect. The rhBMP-2 containing collagen-glycosaminoglycan and collagen-hydroxyapatite scaffolds may be suitable for established nonunion defects.

Summary We have examined the effect of oral monthly ibandronate on distal radius and tibia microarchitecture with high-resolution peripheral quantitative tomography compared with placebo, in women with osteopenia, and found that ibandronate did not significantly affect trabecular bone but improved cortical density and thickness at the tibia. Methods We have examined the effect of ibandronate on bone microarchitecture with peripheral high-resolution quantitative computed tomography (HR-pQCT) in a randomized placebo-controlled trial among 148 women with osteopenia. Patients received either oral 150 mg monthly ibandronate or placebo over 24 months. Bone microarchitecture was assessed at baseline, 6, 12, and 24 months, using HR-pQCT at the distal radius and tibia; areal bone mineral density (aBMD) was measured with DXA at the spine, hip, and radius. Results At 12 months, there was no significant difference in trabecular bone volume at the radius (the primary end point) between women on ibandronate (10.8 ± 2.5%) and placebo (10.5 ± 2.9%), p  = 0.25. There was no significant difference in other radius trabecular and cortical microarchitecture parameters at 12 and 24 months. In contrast, at the tibia, cortical vBMD in the ibandronate group was significantly greater than in the placebo group at 6, 12, and 24 months, with better cortical thickness at 6, 12, and 24 months. With ibandronate, aBMD was significantly increased at the hip and spine at 12 and 24 months but at the radius was significantly superior to placebo only at 24 months. Most of the adverse events related to ibandronate were expected with bisphosphonate use, and none of them were serious. Conclusion We conclude that 12 months of treatment with ibandronate in women with osteopenia did not affect trabecular bone microarchitecture, but improved cortical vBMD at the tibia at 12 and 24 months, and preserved cortical thickness at the tibia.

SummaryIndividual trabecular segmentation was utilized to identify differences in trabecular bone structure in premenopausal women with wrist fractures and non-fracture controls. Fracture subjects had reduced trabecular plate volume, number, thickness, and connectivity. Identifying altered trabecular microarchitecture in young women offers opportunities for counseling and lifestyle modifications to reduce fracture risk.IntroductionPremenopausal women with distal radius fractures (DRF) have worse trabecular bone microarchitecture than non-fracture controls (CONT), yet the characteristics of their trabecular bone structure are unknown.MethodsPremenopausal women with DRF (n = 40) and CONT (n = 80) were recruited. Primary outcome variables included trabecular structure at the distal radius and tibia, assessed by volumetric decomposition of individual trabecular plates and rods from high-resolution peripheral quantitative CT images. Trabecular morphology included plate and rod number, volume, thickness, and connectivity. Areal bone mineral density (aBMD) of the femoral neck (FN aBMD), and ultradistal radius (UDR aBMD) were measured by DXA.ResultsTrabecular morphology differed between DRF and CONT at the radius and tibia (OR per SD decline 1.58–2.7). At the radius, associations remained significant when adjusting for age and FN aBMD (ORs = 1.76–3.26) and age and UDR aBMD (ORs = 1.72–3.97). Plate volume fraction, number and axially aligned trabeculae remained associated with DRF after adjustment for trabecular density (ORs = 2.55–2.85). Area under the curve (AUC) for discriminating DRF was 0.74 for the proportion of axially aligned trabeculae, compared with 0.60 for FN aBMD, 0.65 for UDR aBMD, and 0.69 for trabecular density. Plate number, plate-plate junction, and axial bone volume fraction remained associated with DRF at the tibia (ORs = 2.14–2.77) after adjusting for age, FN aBMD, or UDR aBMD. AUCP.P.Junc.D was 0.72 versus 0.61 for FNaBMD, 0.66 for UDRaBMD, and 0.70 for trabecular density.ConclusionPremenopausal women with DRF have lower trabecular plate volume, number, thickness, and connectivity than CONT. Identification of young women with altered microarchitecture offers opportunities for lifestyle modifications to reduce fracture risk.

Background At present, there is no conclusive evidence regarding the best treatment method for reducible unstable fractures of the distal radius. This study compared the effectiveness of two methods used in surgical treatment of such fractures: percutaneous pinning and external fixation. Methods We randomly allocated 100 patients into two groups treated surgically with modified De Palma percutaneous pinning and bridging external fixation. Independent but not blinded evaluators administered the DASH quality-of-life questionnaire at postoperative months 6 and 24, performed functional assessment of pain, range of motion, and palm grip strength, and radiographic examinations (volar and radial angle, and height of the radius) before the operation, immediately afterwards, and at 6 and 24 months postoperative. Modified De Palma percutaneous pinning patients used an above-elbow cast whereas external fixation group had unrestricted elbow motion after surgery. Patients who for any reason demonstrated treatment failure or required additional interventions were followed up and their results were included in the group into which these patients had initially been randomised according to the intention-to-treat principle. A significance level of 5% (alpha = 0.05). was used for all statistical tests, such that tests presenting a p-value less than 0.05 were considered statistically significant. Results Ninety one (58.8 mean age and 66 participants were female) were included in the final assessment at 24 months. The DASH questionnaire evaluation showed a statistically significant result favouring the De Palma group (mean difference = -7.1 p = 0.044) after six months, but this was not maintained at 24 months. There were no statistically differences between the groups with respect to palm grip strength. Analysis of the range-of-motion limitation index (uninjured side minus affected side motion of) showed a statistical difference (mean difference = 2.4 p = 0.043) favoring the external fixator group with regard to the supination movement 6 months after the operation; however, this was not maintained at 24 months. The final results of the radiographic evaluation were similar for the two groups. Overall, five patients developed complications: two with De Palma pinning and three with external fixation. Conclusion There was a small statistically significant difference favouring the De Palma method in early functional at 6 months according to the DASH questionnaire, and for supination movement favouring the fixator group. However, both were not clinical relevant. By 24 months the groups were similar for all outcomes Trial registration Current Controlled Trials ISRCTN04892785

Background and rationale Fracture incidence increases with ageing and other contingencies. However, the strategy of accelerating fracture repair in clinical therapeutics remain a huge challenge due to its complexity and a long-lasting period. The emergence of nano-based drug delivery systems provides a highly efficient, targeted and controllable drug release at the diseased site. Thus far, fairly limited studies have been carried out using nanomedicines for the bone repair applications. Perfluorocarbon (PFC), FDA-approved clinical drug, is received increasing attention in nanomedicine due to its favorable chemical and biologic inertness, great biocompatibility, high oxygen affinity and serum-resistant capability. In the premise, the purpose of the current study is to prepare nano-sized PFC materials and to evaluate their advisable effects on promoting bone fracture repair. Results Our data unveiled that nano-PFC significantly enhanced the fracture repair in the rabbit model with radial fractures, as evidenced by increased soft callus formation, collagen synthesis and accumulation of beneficial cytokines (e.g., vascular endothelial growth factor (VEGF), matrix metalloprotein 9 (MMP-9) and osteocalcin). Mechanistic studies unraveled that nano-PFC functioned to target osteoblasts by stimulating their differentiation and activities in bone formation, leading to accelerated bone remodeling in the fractured zones. Otherwise, osteoclasts were not affected upon nano-PFC treatment, ruling out the potential target of nano-PFC on osteoclasts and their progenitors. Conclusions These results suggest that nano-PFC provides a potential perspective for selectively targeting osteoblast cell and facilitating callus generation. This study opens up a new avenue for nano-PFC as a promising agent in therapeutics to shorten healing time in treating bone fracture.

Osteoporosis research has focused on vertebral fractures and trabecular bone loss. However, non-vertebral fractures at predominantly cortical sites account for 80% of all fractures and most fracture-related morbidity and mortality in old age. We aimed to re-examine cortical bone as a source of bone loss in the appendicular skeleton. In this cross-sectional study, we used high-resolution peripheral CT to quantify and compare cortical and trabecular bone loss from the distal radius of adult women, and measured porosity using scanning electron microscopy. Exclusion criteria were diseases or prescribed drugs affecting bone metabolism. We also measured bone mineral density of post-mortem hip specimens from female cadavers using densitometry. Age-related differences in total, cortical, and trabecular bone mass, trabecular bone of cortical origin, and cortical and trabecular densities were calculated. We investigated 122 white women with a mean age of 62·8 (range 27–98) years. Between ages 50 and 80 years (n=89), 72·1 mg (95% CI 67·7–76·4) hydroxyapatite (68%) of 106·5 mg hydroxyapatite of bone lost at the distal radius was cortical and 34·3 mg (30·5–37·8) hydroxyapatite (32%) was trabecular; 17·1 mg (11·7–22·5) hydroxyapatite (16%) of total bone loss occurred between ages 50 and 64 years (n=34) and 89·4 mg (83·7–101·1) hydroxyapatite (84%) after age 65 years (n=55). Remodelling within cortex adjacent to the marrow accounted for 49·9 mg (45·4–53·7) hydroxyapatite (47%) of bone loss. Between ages 50–64 years (n=34) and 80 years and older (n=33), cortical density decreased by 127·8 mg (93·1–162·1) hydroxyapatite per cm 3 (15%, p<0·0001) before porosity trabecularising the cortex was included, but 374·3 mg (318·2–429·5) hydroxyapatite per cm 3 (43%, p<0·0001) after; trabecular density decreased by 18·2 mg (−1·4 to 38·2) hydroxyapatite per cm 3 (14%, p=0·06) before cortical remnants were excluded, but 68·7 mg (37·7–90·4) hydroxyapatite per cm 3 (52%, p<0·0001) after. Accurate assessment of bone structure, especially porosity producing cortical remnants, could improve identification of individuals at high and low risk of fracture and therefore assist targeting of treatment. Australia National Health and Medical Research Council.

Summary We compared bone mineral density (BMD) and trabecular bone score (TBS) in postmenopausal women with a distal radius fracture older than 50 years with controls. Total hip BMD was significantly different, but TBS was not different between two groups, suggesting TBS does not reflect microarchitectural changes of the distal radius. Introduction The purpose of this study was to determine whether trabecular bone score (TBS) has additive value for discriminating distal radius fracture (DRF) independent of BMD. Methods We compared BMD and TBS in 258 postmenopausal women with a DRF older than 50 years of age with age- and body mass index (BMI)-matched controls who had no history of osteoporotic fracture. BMD was measured at the lumbar spine and hip using dual energy X-ray absorptiometry scans (GE Lunar Prodigy). TBS was calculated on the same spine image. A multivariate logistic regression analysis was used to analyze the odds ratio (OR) for the occurrence of DRF using age, BMI, lumbar spine BMD, total hip BMD, and TBS. Results Patients with a DRF had significantly lower BMDs at hip (neck, trochanter and total) than those of controls: 0.752 ± 0.097, 0.622 ± 0.089, and 0.801 ± 0.099 in patients and 0.779 ± 0.092, 0.648 ± 0.089, 0.826 ± 0.101 in controls. However, lumbar spine BMD and TBS were not significantly different between the groups ( p  = 0.400 and 0.864, respectively). The multivariate analysis indicated that only total hip BMD was significantly associated with the occurrence of DRF (OR, 10.231; 95 % confidence interval, 1.724–60.702; p  = 0.010). Conclusions TBS was not different between women with a DRF and those without a history of osteoporotic fracture, suggesting that TBS measured at the lumbar spine does not reflect early microarchitectural changes of the distal radius. Only total hip BMD is associated with the risk of DRF in Korean women.