A Novel HR-pQCT Image Registration Approach Reveals Sex-Specific Changes in Cortical Bone Retraction With Aging

During aging, changes in endosteal and periosteal boundaries of cortical bone occur that differ between men and women. We here develop a new procedure that uses high-resolution peripheral quantitative CT (HR-pQCT) imaging and 3D registration to identify such changes within the timescale of longitudinal studies. A first goal was to test the sensitivity of the approach. A second goal was to assess differences in periosteal/endosteal expansion over time between men and women. Rigid 3D registration was used to transform baseline and all follow-up (FU) images to a common reference configuration for which the region consisting of complete slices (largest common height) was determined. Periosteal and endosteal contours were transformed to the reference position to determine the net periosteal and endosteal expansion distances. To test the sensitivity, images from a short-term reproducibility study were used (15 female, aged 21 to 47 years, scanned three times). To test differences between men and women, images from a subset of the Geneva Retirees Cohort were used (248 female, 61 male, average age 65 years, 3.5 and 7 years FU). The sensitivity study indicated a least significant change for detecting periosteal/endosteal expansion of 41/31 microns for the radius and 17/26 microns for the tibia. Results of the cohort study showed significant net endosteal retraction only in females at the radius and tibia after 3.5 years (38.0 and 38.4 microns, respectively) that further increased at 7 years FU (70.4 and 70.8 microns, respectively). No significant net periosteal changes were found for males or females at 7 years. The results demonstrate that it is possible to measure changes in endosteal contours in longitudinal studies within several years. For the investigated cohort, significant endosteal retraction was found in females but not in males. Whether these changes in cortical geometry are related to fracture risk remains to be investigated in larger cohorts © 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).     

The Sydney AFF Score: A Simple Tool to Distinguish Females Presenting With Atypical Femur Fractures Versus Typical Femur Fractures

Atypical femur fractures (AFF) are a rare but serious complication of long-term bisphosphonate use. Although clearly defined by ASBMR criteria, a proportion of patients with AFFs may go unrecognized and the use of qualitative fracture criteria may lead to uncertainty in AFF diagnosis, with significant therapeutic implications. A score that rapidly and accurately identifies AFFs among subtrochanteric femur fractures using quantitative, measurable parameters is needed. In a retrospective cohort of 110 female patients presenting with AFFs or typical femur fractures (TFFs), multiple logistic regression and decision tree analysis were used to develop the Sydney AFF score. This score, based on demographic and femoral geometry variables, uses three dichotomized independent predictors and adds one point for each: (age ≤80 years) + (femoral neck width <37 mm) + (lateral cortical width at lesser trochanter ≥5 mm), (score, 0 to 3). In an independent validation set of 53 female patients at a different centre in Sydney, a score ≥2 demonstrated 73.3% sensitivity and 69.6% specificity for AFF (area under the receiver-operating characteristic curve [AUC] 0.775, SE 0.063) and remained independently associated with AFF after adjustment for bisphosphonate use. The Sydney AFF score provides a quantitative means of flagging female patients with atraumatic femur fractures who have sustained an AFF as opposed to a TFF. This distinction has clear management implications and may augment current ASBMR diagnostic criteria. © 2021 American Society for Bone and Mineral Research (ASBMR).     

High Cardiovascular Risk in Older Men with Poor Bone Microarchitecture—The Prospective STRAMBO Study

Data on the association between bone microarchitecture and cardiovascular disease (CVD) in men are scarce. We studied the link of bone microarchitecture and areal bone mineral density (aBMD) with the risk of major adverse coronary event (MACE) in a cohort of men aged 60 to 87 years followed prospectively for 8 years. At baseline, aBMD was measured using a Hologic Discovery-A device. Bone microarchitecture was assessed at distal radius and tibia by high-resolution peripheral quantitative computed tomography (XtremeCT Scanco device). During the study, 53 men had incident MACE. The analyses were adjusted for confounders related to bone and CVD. In 813 men (53 MACEs), higher aBMD at the lumbar spine, hip, whole body, and radius was associated with lower risk of MACE (hazard ratio [HR] = 0.44–0.71/SD, p < .025 to < .001). In 745 men having valid distal radius scan (47 MACEs), higher cortical density (Ct.BMD) and higher cortical thickness (Ct.Th^d) were associated with lower risk of MACE. This risk was higher in men in the lowest quintile of cortical measures versus the four upper quintiles combined (Ct.BMD: HR = 2.12, 95% confidence interval [CI] 1.08–4.17, p < .025). Findings were similar in 779 men having valid distal tibia scan (48 MACEs). At both sites, higher estimated stiffness and higher failure load were associated with a lower risk of MACE. The risk of MACE was higher in men in the lowest quintile of the measures of bone strength versus four upper quintiles jointly (distal radius stiffness: HR = 2.46, 95% CI 1.27–4.74, p < .01). Similar results were obtained in 638 men without prior fragility fracture and in 689 men without ischemic heart disease at baseline. Thus, in older men followed prospectively for 8 years, higher aBMD, preserved cortical bone status, and higher estimated bone strength were associated with lower risk of MACE after adjustment for relevant confounders. © 2021 American Society for Bone and Mineral Research (ASBMR).     

Development of Hip Bone Geometry During Gender-Affirming Hormone Therapy in Transgender Adolescents Resembles That of the Experienced Gender When Pubertal Suspension Is Started in Early Puberty

Bone geometry can be described in terms of periosteal and endocortical growth and is partly determined by sex steroids. Periosteal and endocortical apposition are thought to be regulated by testosterone and estrogen, respectively. Gender-affirming hormone (GAH) treatment with sex steroids in transgender people might affect bone geometry. However, in adult transgender people, no change in bone geometry during GAH was observed. In this study, we investigated changes in bone geometry among transgender adolescents using a gonadotropin-releasing hormone agonist (GnRHa) and GAH before achieving peak bone mass. Transgender adolescents treated with GnRHa and subsequent GAH before the age of 18 years were eligible for inclusion. Participants were grouped based on their Tanner stage at the start of GnRHa treatment and divided into early, mid, and late puberty groups. Hip structure analysis software calculating subperiosteal width (SPW) and endocortical diameter (ED) was applied to dual-energy X-ray absorptiometry scans performed at the start of GnRHa and GAH treatments, and after ≥2 years of GAH treatment. Mixed-model analyses were performed to study differences over time. Data were visually compared with reference values of the general population. A total of 322 participants were included, of whom 106 were trans women and 216 trans men. In both trans women and trans men, participants resembled the reference curve for SPW and ED of the experienced gender but only when GnRHa was started during early puberty. Those who started during mid and late puberty remained within the reference curve of the gender assigned at birth. A possible explanation might be sought in the phenomenon of programming, which conceptualizes that stimuli during critical windows of development can have major consequences throughout one's life span. Therefore, this study adds insights into sex-specific bone geometry development during puberty of transgender adolescents treated with GnRHa, as well as the general population. © 2021 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.     

中药骨康对去睾大鼠骨质疏松的防治作用

为探讨补肾活血类中药骨康口服液对去睾大鼠所造成的骨质疏松的影响 ,通过切除大鼠睾丸造骨质疏松模型 ,观察了不同剂量中药骨康口服液对该模型大鼠骨面密度 ( ρA ,bone)、骨矿含量 (mM ,bone)及股骨骨生物力学的影响 ,并与特乐定作阳性对照。结果 :中药骨康高、中剂量防治的去睾大鼠股骨扭转试验最大扭矩及血睾酮 (T)含量 ( ρT ,bl)高于模型组 (P <0 .0 5和P <0 .0 1) ,高、中、低剂量组全身及左、右股骨ρA ,bone、mM ,bone高于模型组 (P <0 .0 5 )。提示骨康口服液能提高去睾大鼠血睾酮含量、骨的骨矿含量及骨密度 ,改善骨组织的生物力学性能 ,避免骨折的发生。为中药骨康口服液防治老年男性骨质疏松症提供实验依据。     

股方肌骨瓣移植加内固定治疗青壮年股骨颈头下型骨折

股骨颈骨折较常见于老年人。近年来,随着交通意外及工伤事故的增多,青壮年股骨颈骨折有上升的趋势。股骨颈头下型骨折因部位特殊,影响股骨头的血液供应,骨折后股骨头血供不足,易发生股骨头缺血坏死,其发生率一般为20％－40％「‘」,是骨科治疗的难点。青壮年股骨颈...     

Characterization of Poly(ε-caprolactone)/Polyfumarate Blends as Scaffolds for Bone Tissue Engineering

There is considerable interest in the design of polymeric biomaterials that can be used for the repair of bone defects. In this study, we used ultrasound to prepare a compatibilized blend of poly(ε-caprolactone) (PCL) and poly(diisopropyl fumarate) (PDIPF). The formation of post-sonication inter-polymer coupling products was verified by SEC analysis of a blend with azo-labeled PDIPF. We also analyzed the physicochemical and mechanical properties of the compatibilized blend. When compared to PCL alone, the PCL/PDIPF blend showed no difference in its resistance as evaluated by the elastic modulus, although it did show a 50% decrease in ultimate tensile stress (P < 0.05) and an 84% decrease in elongation-at-break (P < 0.05). However, the mechanical properties of this blend were comparable to those of trabecular bone. We next evaluated biocompatibility of the PCL/PDIPF blend, and of homo-polymeric PCL and PDIPF films for comparison, with UMR106 and MC3T3E1 osteoblastic cells. Osteoblasts plated on the compatibilized blend adhered and proliferated more than on either homo-polymer, showed a greater number of cellular processes with a better organized actin cytoskeleton and expressed more type-I collagen and mineral, both markers of osteoblast phenotype. These results support the hypothesis that this new compatibilized blend could be useful in future applications for bone regeneration.     

Bone Tissue Composition in Postmenopausal Women Varies With Glycemic Control From Normal Glucose Tolerance to Type 2 Diabetes Mellitus

The risk of fragility fracture increases for people with type 2 diabetes mellitus (T2DM), even after controlling for bone mineral density, body mass index, visual impairment, and falls. We hypothesize that progressive glycemic derangement alters microscale bone tissue composition. We used Fourier-transform infrared (FTIR) imaging to analyze the composition of iliac crest biopsies from cohorts of postmenopausal women characterized by oral glucose tolerance testing: normal glucose tolerance (NGT; n = 35, age = 65 ± 7 years, HbA1c = 5.8 ± 0.3%), impaired glucose tolerance (IGT; n = 26, age = 64 ± 5 years, HbA1c = 6.0 ± 0.4%), and overt T2DM on insulin (n = 25, age = 64 ± 6 years, HbA1c = 9.13 ± 0.6). The distributions of cortical bone mineral content had greater mean values (+7%) and were narrower (−10%) in T2DM versus NGT groups (p < 0.05). The distributions of acid phosphate, an indicator of new mineral, were narrower in cortical T2DM versus NGT and IGT groups (−14% and −14%, respectively) and in trabecular NGT and IGT versus T2DM groups (−11% and −10%, respectively) (all p < 0.05). The distributions of crystallinity were wider in cortical NGT versus T2DM groups (+16%) and in trabecular NGT versus T2DM groups (+14%) (all p < 0.05). Additionally, bone turnover was lower in T2DM versus NGT groups (P1NP: −25%, CTx: −30%, ucOC: −24%). Serum pentosidine was similar across groups. The FTIR compositional and biochemical marker values of the IGT group typically fell between the NGT and T2DM group values, although the differences were not always statistically significant. In summary, worsening glycemic control was associated with greater mineral content and narrower distributions of acid phosphate, an indicator of new mineral, which together are consistent with observations of lower turnover; however, wider distributions of mineral crystallinity were also observed. A more mineralized, less heterogeneous tissue may affect tissue-level mechanical properties and in turn degrade macroscale skeletal integrity. In conclusion, these data are the first evidence of progressive alteration of bone tissue composition with worsening glycemic control in humans. © 2020 American Society for Bone and Mineral Research (ASBMR).     

A collagen–phosphophoryn sponge as a scaffold for bone tissue engineering

Non-collagenous phosphoproteins that interact with a type-I collagen are thought to nucleate bone mineral into collagen networks of mineralized tissues. Previously, phosphophoryn cross-linked to type-I collagen was reported to be an effective nucleator of appatite. However, free phosphophoryn molecules inhibit the formation of apatite in vitro. On the basis of the above study, we expected a collagen-phosphophoryn sponge to be a good scaffold for bone-tissue engineering and examined the formation of bone in orthotopically transplanted composites of the sponge and bone marrow osteoblasts in vivo in Fischer rats. Osteoblastic primary cells were obtained from the bone shaft of femorae of Fisher rats, according to the method of Maniatopoulous et al. A suspension of marrow cells was distributed through a flask with standard culture medium and incubated at 37°C. When cultures were nearly confluent after 10 days, they were concentrated by centrifugation to 10⁶ cells/ml and subcultured onto the synthesized collagen-phosphophoryn sponge and a collagen sponge (control). After 14 days, the composites of collagen-phosphophoryn and osteoblastic cells as well as control composites were transplanted into bone-defect sites of Fisher rats (holes 2 mm in diameter) and then the wounds were sutured. The composites were harvested at 1-8 weeks after implantation, and stained with hematoxylin and eosin. It was found that more bone was formed in the composites of collagen-phosphophoryn sponge and osteoblasts than control composites from 1 week to 8 weeks, suggesting that the collagen-phosphophoryn sponge is a good candidate as a scaffold for bone-tissue engineering.