QCT measures of bone strength at the thoracic and lumbar spine: the Framingham Study

We used volumetric quantitative computed tomography (QCT) scans to evaluate volumetric bone density (vBMD), geometry, and strength in the thoracic (T8 to T10) and lumbar (L3 to L5) spine and determined how these parameters varied with age, sex, and spinal region. Participants included 690 participants of the Framingham Study, 40 to 87 years old (mean, 61 years). In both women and men, trabecular vBMD declined with age similarly for lumbar and thoracic regions, whereas cortical vBMD and integral vBMD, vertebral strength, and compressive force declined more at the lumbar spine than thoracic spine (interaction, p < 0.01). Notably, in men, cortical vBMD increased (β = 0.0004, p = 0.01), and vertebral strength did not change (β = 1.9305, p = 0.66) at the thoracic spine with age. In both women and men, vertebral cross-sectional area increased less and the factor-of-risk increased more with age at the lumbar than at the thoracic region (interaction, p < 0.01). For example, in women, the factor-of-risk for forward flexion increased (worsened) with age 6.8-fold more in the lumbar spine (β = 0.0157), compared with the thoracic spine (β = 0.0023). vBMD and vertebral strength declined more and the factor-of-risk increased more with age in women than men (interaction, p < 0.01). For instance, integral vBMD for the lumbar spine declined 36% from 40 to 75 years of age in women compared with 18% in men. There was little or no age-related change in the forces applied to the thoracic vertebrae in either women or men. Age-related changes were greater in the lumbar spine than in the thoracic region and greater in women than men. Whereas women lost bone density and strength at both the thoracic and lumbar spine, in men, vertebral strength declined only at the lumbar spine. Our study confirms the importance of evaluating determinants of vertebral strength in both the thoracic and lumbar spine and in both women and men to understand mechanisms underlying the structural failure of vertebral bodies with aging.     

Does osteoporosis therapy invalidate FRAX for fracture prediction?

Ten-year fracture risk assessment with the fracture risk assessment system (FRAX) is increasingly used to guide treatment decisions. Osteoporosis pharmacotherapy reduces fracture risk, but the effect is greater than can be explained from the increase in bone mineral density (BMD). Whether this invalidates fracture predictions with FRAX is uncertain. A total of 35,764 women (age ≥50 years) and baseline BMD testing (1996–2007) had FRAX probabilities retroactively calculated. A provincial pharmacy database was used to identify osteoporosis medication use. Women were categorized as untreated, current high adherence users [medication possession ratio (MPR) ≥0.80 in the year after BMD testing], current low adherence users (MPR <0.80), and past users. Fractures outcomes to 10 years were established form a population-based health data repository. FRAX and femoral neck BMD alone stratified major osteoporotic and hip fracture risk within untreated and each treated subgroup (all p-values <0.001) with similar area under the receiver operating characteristic curve. In untreated and each treated subgroup, a stepwise gradient in observed 10-year major osteoporotic and hip fracture incidence was found as a function of the predicted probability tertile (all p-values <0.001 for linear trend). Concordance (calibration) plots for major osteoporotic fractures and hip fractures showed good agreement between the predicted and observed 10-year fracture incidence in untreated women and each treated subgroup. Only in the highest risk tertile of women highly adherent to at least 5 years of bisphosphonate use was observed hip fracture risk significantly less than predicted, though major osteoporotic fracture risk was similar to predicted. In summary, this work suggests that the FRAX tool can be used to predict fracture probability in women currently or previously treated for osteoporosis. Although FRAX should not be used to assess the reduction in fracture risk in individuals on treatment, it may still have value for guiding the need for continued treatment or treatment withdrawal     

Effect of Heparin on Dextran Sulfate Sodium-Induced Colitis

Heparin has been shown to ameliorateinflammatory bowel disease in several series. Inaddition to its anticoagulant properties, heparin hasnumerous other effects that may be beneficial ininflammatory bowel disease. Other sulfated polysaccharides,such as dextran sulfate, cause colitis in mice throughunknown mechanisms. We postulate that dextran sulfateand heparin may act via similar pathways with opposite effects. To examine this thesis, theeffect of heparin on dextran sulfate-induced colitis wasstudied. Swiss-Webster mice were given 5% dextransulfate in their drinking water for five days to induce colitis. Heparin was given boththerapeutically after the induction of colitis andprophylactically by subcutaneous injections, with salineinjections given in controls. Histologic sections ofcolon were randomized and graded for colitis.Heparinized animals showed no significant difference inthe pattern or severity of colitis when compared tocontrol animals. It is concluded that heparin does not ameliorate the murine colitis induced bydextran sulfate in the doses given.     

髌骨的生物力学实验研究

用三维光弹实验方法和有限元分析法,分析髌骨在正常单足站立位屈膝15°、30°、45°、60°、75°、90°等状态下的应力分布规律。结果显示:随着屈膝度增加,髌骨明显变为一受弯构件,其表面中部承受拉应力最大,髌底髌尖次之,髌骨后部承受压应力。屈膝90°时拉压应力均最大。额状面上髌骨的主拉应力迹线略呈“V”形,且受Q角影响而不同程度地向外偏移,屈膝30°时偏移最显著。     

麦饭石对骨折愈合过程影响的实验研究

提要从生物力学及组织学角度观察了麦饭石对骨折愈合过程的影响。强度测试结果表明:用药组的拉伸、弯曲破坏载荷及拉伸、弯曲强度均比对照组高(P<0.05～0.01)。病理报告提示:用药组与对照组比较断端血肿吸收快,同一期内肉芽组织转变为骨样组织多,连接快,软骨骨化少,骨改建早。表明麦饭石不仅能提高骨折愈合质量,而且加快了骨折愈合速度,是促进骨折愈合的有效药物。     

重组人生长激素对人结肠癌移植瘤裸鼠CEA,cAMP及cGMP的影响

目的　建立人结肠癌细胞株COLO 3 2 0裸鼠移植瘤模型 ,探讨重组人生长激素 (γ hGH )对血清癌胚抗原 (CEA)、移植瘤中CEA、环磷酸腺苷 (cAMP)及环磷酸鸟苷 (cGMP)的影响。方法　经 4次传代 ,将生长稳定的 2 0只荷瘤裸鼠随机分为 4组 :( 1)对照组 ;( 2 )γ hGH组 ;( 3 )羟基喜树碱 (CPT )组 ;( 4 )γ hGH +CPT组 (联合组 )。接种次日开始给药 ,连续用药 3 5d后处死裸鼠 ,留取裸鼠血及移植瘤标本 ,测定血清及瘤组织中CEA ,瘤组织中cAMP及cGMP的含量。结果　γ hGH组移植瘤与对照组移植瘤比较 ,所有指标的差异均无统计学意义 (P >0 .0 5 ) ;γ hGH组与CPT组及联合组比较 ,所有指标的差异均有统计学意义 (P <0 .0 0 1) ;而GPT组与联合组间无显著性差异 (P >0 .0 5 )。结论　γ hGH对人结肠癌细胞株COLO 3 2 0移植瘤模型的CEA ,cAMP ,cGMP无影响。     

More forearm fractures among urban than rural women: The NOREPOS study based on the Tromsø study and the HUNT study

Higher rates of hip fracture and all fractures combined have been observed in urban compared with rural areas, but whether there are urban‐rural differences in distal forearm fracture rates is less studied. The aim of this longitudinal study was to compare the incidence of forearm fracture in postmenopausal women in urban and rural areas in Norway and to investigate risk factors that could explain potential fracture differences. The study included data from 11,209 women aged 65 years or more who participated in two large health studies, the Tromsø Health Study in 1994–1995 and the Nord‐Trøndelag Health Study in 1995–1997. Forearm bone mineral density (BMD) was measured by single‐energy X‐ray absorptiometry in a subsample of women (n = 7333) at baseline. All women were followed with respect to hospital‐verified forearm fractures (median follow‐up 6.3 years). A total of 9249 and 1960 women lived in areas classified as rural and urban, respectively. Urban women had an increased forearm fracture risk [relative risk (RR) = 1.29, 95% confidence interval (CI) 1.09–1.52] compared with women in rural areas. Rural women had higher body mass index (BMI) than urban women, and the RR was moderately reduced to 1.21 (95% CI 1.02–1.43) after BMI adjustments. Rural women had the highest BMD. In the subgroup with measured BMD, adjustments for BMD changed the urban versus rural RR from 1.21 (95% CI 0.96–1.52) to 1.05 (95% CI 0.83–1.32), suggesting that BMD is an important explanatory factor. In conclusion, higher rates of forearm fractures was found in urban compared with rural women. © 2011 American Society for Bone and Mineral Research.     

Saturated and Unsaturated Bone Marrow Lipids Have Distinct Effects on Bone Density and Fracture Risk in Older Adults

Greater bone marrow adiposity (BMAT) is associated with lower bone mineral density (BMD) and vertebral fractures; less is known about BMAT composition and bone. We studied BMAT composition and bone outcomes in 465 participants from the Age Gene/Environment Susceptibility (AGES)-Reykjavik study. BMAT saturation and unsaturation, measured with magnetic resonance spectroscopy, were defined as the ratio of saturated (1.3 ppm peak) or unsaturated (5.3 ppm peak) lipid to total marrow contents, respectively. At baseline and follow-up visits, spine and hip BMD were assessed with quantitative computed tomography (QCT) and dual-energy X-ray absorptiometry (DXA) and vertebral fractures were identified with DXA. Incident clinical fractures were identified through medical records for up to 8.8 years of follow-up. Associations between BMAT composition and BMD, bone loss, and fractures were evaluated in adjusted regression models. At baseline, mean ± standard deviation (SD) participant age was 81.7 ± 4.3 years, mean BMAT unsaturation was 3.5% ± 1.0%, and mean saturation was 46.3% ± 7.2% in the full cohort (47.7% women). Each SD increase in BMAT saturation was associated with lower trabecular BMD: −23.6% (spine) and −13.0% (total hip) (all p < 0.0001). Conversely, BMAT unsaturation (per SD increase) was associated with higher trabecular BMD: +17.5% (spine) and +11.5% (total hip) (all p < 0.001). BMAT saturation (per SD increase) was associated with greater risk for prevalent (odds ratio [OR] 1.46; 95% confidence interval [CI], 1.11–1.92) and incident (OR 1.55; 95% CI, 1.03–2.34) vertebral fracture. BMAT unsaturation (per SD increase) was associated with lower risk for incident vertebral fracture (OR 0.58; 95% CI, 0.38–0.89). In gender stratified analyses, BMAT saturation and unsaturation had opposite associations with incident clinical fracture among men. In general, saturated marrow lipids were associated with worse skeletal outcomes, whereas unsaturated lipids were associated with better outcomes. We recommend that future studies of marrow fat and skeletal health report measurements of saturated and unsaturated marrow lipids, rather than total marrow fat content alone. © 2022 American Society for Bone and Mineral Research (ASBMR).     

Sclerostin Antibody Administration Converts Bone Lining Cells Into Active Osteoblasts

Sclerostin antibody (Scl‐Ab) increases osteoblast activity, in part through increasing modeling‐based bone formation on previously quiescent surfaces. Histomorphometric studies have suggested that this might occur through conversion of bone lining cells into active osteoblasts. However, direct data demonstrating Scl‐Ab‐induced conversion of lining cells into active osteoblasts are lacking. Here, we used in vivo lineage tracing to determine if Scl‐Ab promotes the conversion of lining cells into osteoblasts on periosteal and endocortical bone surfaces in mice. Two independent, tamoxifen‐inducible lineage‐tracing strategies were used to label mature osteoblasts and their progeny using the DMP1 and osteocalcin promoters. After a prolonged “chase” period, the majority of labeled cells on bone surfaces assumed a thin, quiescent morphology. Then, mice were treated with either vehicle or Scl‐Ab (25 mg/kg) twice over the course of the subsequent week. After euthanization, marked cells were enumerated, their thickness quantified, and proliferation and apoptosis examined. Scl‐Ab led to a significant increase in the average thickness of labeled cells on periosteal and endocortical bone surfaces, consistent with osteoblast activation. Scl‐Ab did not induce proliferation of labeled cells, and Scl‐Ab did not regulate apoptosis of labeled cells. Therefore, direct reactivation of quiescent bone lining cells contributes to the acute increase in osteoblast numbers after Scl‐Ab treatment in mice. © 2016 American Society for Bone and Mineral Research.     

Bisphosphonate Withdrawal: Effects on Bone Formation and Bone Resorption in Maturing Male Mice

Bisphosphonates are being increasingly used to treat pediatric patients with skeletal disorders. However, the effects of long‐term bisphosphonate therapy and cessation of therapy during growth are unclear. Thus, studies were undertaken to determine the effects of alendronate discontinuation after treatment of C57Bl/6 mice during the period of rapid skeletal growth. Compared with vehicle‐treated mice, 16 weeks of alendronate treatment starting at age 18 days resulted in a 3.7‐fold increase in trabecular bone in the setting of suppressed bone formation. Alendronate therapy for 8 weeks followed by 8 weeks of vehicle treatment resulted in a more pronounced increase in trabecular bone compared with mice treated with alendronate for 16 weeks (1.7‐fold) and to vehicle‐treated controls (6.5‐fold). Mice that received alendronate for 8 weeks followed by 8 weeks of vehicle exhibited increased osteoblast surface (2.5‐fold), mineralizing surface (5.7‐fold), and bone formation rate (5.1‐fold) compared with mice treated continuously with alendronate. However, these parameters were not restored to the levels observed in the vehicle‐treated mice. Thus, partial resumption of bone formation upon cessation of bisphosphonate therapy leads to a greater increase in trabecular bone than that found when bisphosphonates are administered continuously to growing mice. These data suggest that intermittent administration of bisphosphonates may optimize their beneficial effects on the growing skeleton. © 2017 American Society for Bone and Mineral Research.