Bone Mass Measurements Research Articles

Measuring Bone Volume at Multiple Densities by Micro-computed Tomography.

Bone strength is controlled by both bone mass, and the organization and quality of the bone material. The current standard method for measuring bone mass in mouse and rat studies is micro-computed tomography. This method typically uses a single threshold to identify bone material in the cortical and trabecular regions. However, this single threshold method obscures information about the mineral content of the bone material and depends on normal morphology to separately analyze cortical and trabecular structures. To extend this method to identify bone mass at multiple density levels, we have established a protocol for unbiased selection and application of multiple thresholds using a standard laboratory-based micro-computed tomography instrument. This non-invasive method can be applied to longitudinal studies and archived samples and provides additional information about bone structure and strength.

Bone Strength/Bone Mass Discrepancy in Glucocorticoid-Treated Adult Mice.

ABSTRACTGlucocorticoids increase bone fragility in patients in a manner that is underestimated by bone mass measurement. This study aimed to determine if the adult mouse could model this bone strength/bone mass discrepancy. Forty‐two 13‐week‐old BALB/cJ mice were randomized into vehicle and glucocorticoid groups, implanted with vehicle or 6‐methylprednisolone pellets, and necropsied after 60 and 120 days. Bone strength and bone mass/microarchitecture were assessed at the right central femur (CF; cortical‐bone–rich) and sixth lumbar vertebral body (LVB6; trabecular‐bone–rich). Bound water (BW) of the whole right femur was analyzed by proton‐nuclear magnetic resonance (1H‐NMR) relaxometry. Data were analyzed by two‐factor ANOVA with time (day 60 and day 120) and treatment (vehicle and glucocorticoid) as main effects for all data. Significant interactions were further analyzed with a Tukey's post hoc test. Most bone strength measures in the CF were lower in the glucocorticoid group, regardless of the duration of treatment, with no time × treatment interaction. However, bone mass measures in the CF showed a significant time × treatment interaction (p = 0.0001). Bone strength measures in LVB6 showed a time × treatment interaction (p < 0.02) such that LVB6 strength was lower after 120 days of glucocorticoids compared with 120 days of vehicle treatment. Whole‐femur–BW was lower with both glucocorticoid treatment (p = 0.0001) and time (p < 0.02), with a significant time × treatment interaction (p = 0.005). Glucocorticoid treatment of male BALB/cJ mice resulted in the lowering of bone strength in both cortical and trabecular bone that either appeared earlier or was greater than the treatment‐related changes in bone mass/microarchitecture. The adult mouse may be a good model for investigating the bone strength/mass discrepancy observed in glucocorticoid‐treated patients. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

An MSC bone-homing compound, Rab001, increases bone mass and reduces the incidence of osteonecrosis in a glucocorticoid-induced osteonecrosis mouse model.

Currently, there are no effective medications to either prevent or slow the progression of atraumatic osteonecrosis (ON).The objective of this study is to determine the effects of bone-targeted delivery of mesenchymal stem cells on the prevalence of ON in a glucocorticoid (GC)-induced mouse model. Eight-week-old male BALB/c mice were randomized into groups that received placebo (PL), prednisolone (GC), or concurrent treatments with GC+mesenchymal stromal cells (MSCs), Rab001 or GC+Rab001 + MSCs. Human parathyroid hormone (hPTH) was used as a positive control for bone anabolism. Mice were killed after 30days, and quantitative measurements of bone mass, bone strength, prevalent ON at the distal femoral epiphysis (DFE) were performed. Angiogenesis was accessed by RNA-Seq, the circulating angiogenic markers, as well as by immunohistochemical staining. We have showed that a novel agent, Rab001 that can noncovalently bind to mesenchymal stem cells (MSC) and direct them to the bone, prevents the incidence of glucocorticoid-induced osteonecrosis in the mouse. In contrast, PTH, a bone anabolic treatment, preserves bone mass but sustains higher ON incidence than Rab001+/- MSC-treated mice. The results of these experiments reveal that glucocorticoids increase the prevalence of ON, and agents that prevent loss of bone vascularity appear to prevent the development of ON. This intervention might be useful in patients with early stages of atraumatic ON.

The Relationship Of Insulin‑Like Growth Factor 1 With Bone Mass In Obese Female

This study aimed to analyze the relationship of insulin-like growth factor 1 with bone mass in obese female. This study used a cross sectional study method using 30 obese women aged 19-23 years, body mass index (BMI) 25-35 kg / m2, normal blood pressure, normal resting heart rate (RHR), normal hemoglobin (Hb). and fasting blood glucose (FBG) &lt;100 mg / dL. Measurement of IGF-1 levels used the Enzym Link Immunosorbent Assay (ELISA) method. Measurement of bone mass using TANITA (Body Composition Analyzer DC3607601 (2) -1604 FA, TANITA Corporation of America, Inc., USA). The data analysis technique used the Pearson product-moment test with Statistical Package for Social Science (SPSS). The results showed that mean levels of IGF-1 (1.17 ± 0.10) ng / mL and bone mass (2.49 ± 0.06) kg (r = 0.712, P ≤ 0.001). Our findings suggest that there was a positive correlation between IGF-1 levels and bone mass

Systemic osteoprotegerin does not improve peri-implant bone volume or osseointegration in rabbits.

Anti-RANKL (receptor activator of nuclear factor kappa-B ligand) agents function by blocking the differentiation of osteoclasts, thereby proving useful in the clinical management of postmenopausal osteoporosis. The effects of such agents on osseointegration is less well understood. The purpose of the current study was to investigate whether osteoprotegerin (OPG), an osteoclast inhibitor, enhances the known anabolic effects of mechanical loading (VEH) and intermittent PTH (iPTH) using a well-established rabbit model of osseointegration. In the first set of experiments, OPG was administered either alone or combined with iPTH to study its effects on measured bone mass. The second set of experiments was conducted using a higher dosage of OPG (10 mg/kg) to explore its early impact at the cellular and molecular levels. All subjects had mechanical load applied to the implant on one extremity, and no load applied on the contralateral side. In the first set of experiments, OPG alone decreased peri-implant bone mass compared to the mechanical loading group, whereas OPG + iPTH increased peri-implant bone mass compared to the OPG group. In the second set of experiments, high-dose OPG significantly decreased osteoclast number (-74.3%) at 1 week. However, this effect was not sustained as osteoclast number returned to baseline by 2 weeks. These results suggest that systemic administration of OPG does not enhance osseointegration, but rather has a detrimental effect.

Impact microindentation in men with impaired fasting glucose and type 2 diabetes.

Individuals with type 2 diabetes (T2DM) are at increased fracture risk, with bone mineral density (BMD) measurements underestimating risk. Impact microindentation (IMI), a technique that measures bone microindentation distances, expressed as bone material strength index (BMSi), may improve fracture risk estimation in individuals with T2DM. This study describes the relationship between BMSi and glycaemia status in men and makes a comparison with bone measures from dual energy X-ray absorptiometry (DXA). Participants were 340 men aged 33-96yr from the Geelong Osteoporosis Study. Impaired fasting glucose (IFG) was defined using fasting plasma glucose (FPG) between 5.5 and 6.9mmol/L. Diabetes was defined as FPG≥7.0mmol/L, use of antihyperglycemic medication and/or self-report. Two participants with type 1 diabetes were excluded. BMSi was measured using an OsteoProbe. Femoral neck (FNBMD) and lumbar spine (LSBMD) were measured using DXA (Lunar Prodigy) and trabecular bone score (TBS) was calculated (TBS iNsight Version 2.2). Using linear regression techniques, the relationship between glycaemia status and BMSi was evaluated, adjusting for other potential confounders (including lifestyle factors, clinical measurements and FNBMD). Glycaemia status was also considered as a binary variable (T2DM vs normoglycaemia and IFG). There were 234 (68.8%) men with normoglycaemia, 59 (17.4%) with IFG and 47 (13.8%) with diabetes. When considering glycaemia status as a binary variable, men with T2DM had lower mean BMSi compared to those without T2DM (normoglycaemia and IFG combined) (79.8; 95%CI 77.0-82.6 vs 83.0; 82.2-83.8 p=0.043) and this difference in BMSi was independent of FNBMD. No differences were observed for either FNBMD or LSBMD; however, TBS was lower (1.177; 1.121-1.233 vs 1.256; 1.240-1.272, p=0.015, independent of FNBMD). For glycaemia status considered in three groups, there were no differences in mean BMSi values between men with normoglycaemia, IFG and T2DM (82.9 (95%CI 82.0-83.8), 83.5 (81.8-85.2) and 79.8 (77.0-82.6), respectively; ANCOVA, p=0.104). Measures reflecting bone material properties and microarchitecture (BMSi and TBS) might be better than measures of bone mass (BMD) in identifying individuals with T2DM at risk of fracture.

Calcium repletion to rats with calcipenic rickets fails to recover bone quality: A calcipenic “memory”

Calcipenic rickets is prevalent in underprivileged children in developing countries. Calcipenic rickets resulting from dietary calcium (Ca) deficiency decreases bone mass and deteriorates bone microstructure in humans. The effect of dietary Ca replenishment (CaR) on rachitic bones in animal models depends on the amount, critical period and duration of replenishment, however, the extent of recovery in various bone parameters including bone quality remains unclear. We investigated the effect of CaR in rat skeleton after inducing calcipenic rickets. Female SD rats (postnatal 28days/P28) were rendered calcipenic by feeding calcium deficient (CaD) diet (0.1% Ca) till P70 while control SD rats were fed Ca sufficient diet (0.8% Ca). At P70, calcipenic rats were switched to 0.8% Ca diet till P150 for one group and P210 for another group (endpoint). The CaD groups received 0.1% Ca diet throughout the study (P210). In the CaD groups, serum Ca and phosphate, and bone mineral density (BMD) were significantly decreased whereas serum alkaline phosphatase (ALP), iPTH and CTX-1 were increased compared to age-matched controls. Moreover, at the endpoint, the CaD group had reduced bone mass, surface referent bone formation parameters, tissue mineralization and strength accompanied by the increased osteoid thickness and microarchitectural decay (measured by trabecular geometric parameters) with poor crystal packing. The CaR group showed complete recovery in serum Ca, iPTH, ALP and CTX-1, and BMD, however, the bone quality parameters including bone strength, microarchitectural decay, tissue mineralization, and crystallinity were incompletely restored. Decreased surface referent bone formation and increased unmineralized bones (osteoid) indicative of osteomalacia were also observed in the CaR group at P210 compared with control despite prolonged replenishment. We conclude that a prolonged Ca repletion following the induction of calcipenic rickets in rats although shows the recovery of biochemical measures of bone metabolism and bone mass, however, the bone quality remains compromised. This suggests that a "memory" of calcipenia occurring at the early growth stage persists in the skeleton of adult rats despite a prolonged Ca replenishment.

History of alendronate.

Alendronate was synthesized in 1970s in a search for inhibitors of calcification. Istituto Gentili investigators identified it as a potent inhibitor of bone resorption and obtained a patent covering its use in the treatment of osteoporosis and other disorders of excessive bone resorption in the 1980s. Merck licensed alendronate in 1988 and its pharmaceutical chemists reformulated it as a sodium salt with good solubility in a tablet that reduced its potential for esophageal irritation. Clinical trials proved that it reduced bone turnover, increased BMD and reduced the risk of vertebral fractures in postmenopausal osteoporotic women. Merck sponsored a large clinical trials that won FDA approval for treatment of osteoporosis in postmenopausal women and showed that it reduced the risk of spine and hip fractures. Its approval in the US in 1995 spurred sales of bone densitometers and BMD testing to screen for low bone mineral density and identify osteoporosis. Bone mass measurement was supported by medical society guidelines and reimbursement by Medicare and other insurers in the USA. A 70 mg weekly instead of 10 mg daily dose of alendronate produced the same effect on BMD and biochemical markers of bone remodelling with greater convenience and reduced potential for upper GI adverse events. Consequently, by 2006, about 30 million prescriptions for alendronate were written annually in the U.S. for about 15% of postmenopausal women in the U.S. Thereafter, publicity about rare but concerning atypical femoral fractures (AFF) and osteonecrosis of the jaw (ONJ) along with the expiry of Merck's patent (in 2008) and cessation of their promotion of alendronate, and a decline in use of densitometry led to a steady slide in its use even among patients for whom the benefits of alendronate far outweigh its potential risks. Nevertheless, in 25years since its regulatory approval, alendronate has undoubtedly prevented millions of fractures world-wide.

Edible Bird's Nest Attenuates Menopause-Related Bone Degeneration in Rats via Increaing Bone Estrogen-Receptor Expression.

To investigate the mechanistic basis for the attenuation of bone degeneration by edible bird's nest (EBN) in ovariectomized rats. Forty-two female Sprage-Dawley rats were randomized into 7 groups (6 in each group). The ovariectomized (OVX) and OVX + 6%, 3%, and 1.5% EBN and OVX +estrogen groups were given standard rat chow alone, standard rat chow +6%, 3%, and 1.5% EBN, or standard rat chow +estrogen therapy (0.2mg/kg per day), respectively. The sham-operation group was surgically opened without removing the ovaries. The control group did not have any surgical intervention. After 12 weeks of intervention, blood samples were taken for serum estrogen, osteocalcin, and osteoprotegerin, as well as the measurement of magnesium, calcium abd zinc concentrations. While femurs were removed from the surrounding muscles to measure bone mass density using the X-ray edge detection technique, then collected for histology and estrogen receptor (ER) immunohistochemistry. Ovariectomy altered serum estrogen levels resulting in increased food intake and weight gain, while estrogen and EBN supplementation attenuated these changes. Ovariectomy also reduced bone ER expression and density, and the production of osteopcalcin and osteorotegerin, which are important pro-osteoplastic hormones that promote bone mineraliztion and density. Conversely, estrogen and EBN increased serum estrogen levels leading to increased bone ER expression, pro-osteoplastic hormone production and bone density (all P<0.05). EBN could be used as a safe alternative to hormone replacement therapys for managing menopausal complications like bone degeneration.

Regional changes in indices of bone strength of upper and lower limbs in response to high-intensity impact loading or high-intensity resistance training

It is well known that the bone response to physical activity is highly dependent on the nature of the loads imposed. Despite this, few direct comparisons of the effect of impact-style loading and resistance training on bone have been made. We therefore aimed to compare the effects of 10-month, twice-weekly, high-impact loading and 10-month, twice-weekly, high-intensity resistance training on indices of bone strength of both the upper and lower limbs of young adult women. Physically inactive, otherwise healthy, young adult women (18-30years) with below average bone mass (T-score≤0) were recruited as part of the OPTIMA-Ex trial. Testing included DXA- and pQCT-derived measures of bone mass and indices of bone strength and QUS-derived measures of bone quality of the dominant (D) and non-dominant (ND) upper (radius) and lower limbs (femoral neck, tibia, calcaneus). The present study examined those participants who completed the impact training (IT; n=10) and resistance training (RT; n=12) arms of the trial. Age differed between groups at baseline (IT=23.2±3.8years, RT=20.5±1.8years; p=0.042). Compliance with the training programs did not differ (IT=61.4±15.1%, RT=66.4±11.2%, p=0.381). Age and baseline differences in bone outcomes served as covariates for repeated measures and univariate ANCOVA conducted for dependent variables and percent change respectively. IT improved distal pQCT-derived bone mineral density (BMD) of the upper limb (ND radius: total BMD=8.55±2.26% versus 1.50±2.04%, p=0.040 and trabecular BMD=1.86±0.90% versus -1.30±0.81%, p=0.029) and lower limb (ND tibia trabecular BMD=1.22±0.55% versus -0.82±0.50%, p=0.017), more than RT. IT also improved upper limb bone strength index (BSI) (ND radius total BSI=15.35±2.83% versus 2.67±2.55, p=0.005) and lower limb BSI (D tibia total BSI=5.16±1.13% versus 0.37±1.02%, p=0.008; D tibia trabecular BSI=3.93±1.76% versus -2.84±1.59, p=0.014, ND tibia trabecular BSI=3.57±1.63% versus -3.15±1.48%, p=0.009) more than RT. Conversely, RT improved DXA-derived cortical volumetric BMD at the femoral neck more than IT (3.68±1.99% versus -4.14±2.20%, p=0.021). Results suggest that IT and RT provide differing site-specific effects in both the upper and lower limbs, with superior bone responses observed at the distal segment from IT, while RT appeared to have greater effect on the shaft of the bone, on indices of bone-strength in young adult women.

Diagnostic Value of Mid-Thigh and Mid-Calf Bone, Muscle, and Fat Mass in Osteosarcopenia: A Pilot Study.

Osteosarcopenia is defined as the concomitant occurrence of osteoporosis and sarcopenia. Current lack of consensus on sarcopenia definitions, combined with the low sensitivity andspecificity of screening methodologies, has resulted in varying prevalences of sarcopenia, and consequently osteosarcopenia diagnosis. Previous research indicates that mid-thigh is a potential surrogate region for the assessment of bone, muscle, and fat mass in a single,efficient and low-radiation dual x-ray absorptiometry (DXA) scan. We hypothesized that muscle and bone mass measurements in the mid-thigh region can be used to evaluate bone and muscle health and function. A retrospective study was conducted on community-dwelling older subjects (> 65 y.o., n = 260) who were at risk of falls and fractures. Mid-thigh and mid-calf bone, lean muscle, and fat masses, as well as their association with muscle function, falls, and fractures were compared against conventional measures (hip/spine bone, appendicular lean, and gynoid/android fat masses). Mid-thigh bone, lean, and fat masses showed strong correlation with conventional measures. Mid-thigh lean mass showed similar associations with grip strength, gait speed, and timed up and go (TUG) test as appendicular lean mass. Appendicular, mid-thigh and mid-calf lean masses corrected for body mass index (BMI) showed stronger associations than when corrected for height2. None of the indices were associated with fractures; but fat mass was invariably associated with falls. Those with falls and fractures history had lower bone and muscle mass at mid-thigh. Mid-thigh is a potential new surrogate to study bone, muscle, and fat mass in older people, with comparable ability in predicting muscle performance and falls.

Diet Quality in Relation to Fat, Lean, and Bone Mass in Children: A Population-based Study (P18-105-19)

ObjectivesNutrition in early life is considered a crucial modifiable determinant of growth and development. Still, whether overall diet quality in childhood is related to body composition and bone health remains unclear. We aimed to examine associations of overall diet quality with detailed measures of fat, lean, and bone mass in childhood. MethodsWe included 3991 children from a large population-based prospective cohort in the Netherlands. Dietary intake was assessed using a food-frequency questionnaire at their age of 8 years, and a diet quality score (0–10) was calculated, measuring adherence to age-specific dietary guidelines. Height, weight, and detailed body composition of the children were measured at their age of 10 years. Body composition was assessed using dual-energy X-ray absorptiometry. We calculated sex- and age-specific SD-scores for body mass index (BMI), fat mass index (FMI), fat-free mass index (FFMI), bone mineral density (BMD), bone mineral content (BMC), and area-adjusted BMC (aBMC). ResultsMean diet quality score of the children was 4.5 (±1.2) out of 10, and 12.4% of the children had overweight. After adjustment for socioeconomic and lifestyle factors, we observed that a higher diet quality was associated with a higher height, weight, and BMI in childhood. This positive association of diet quality with BMI was fully driven by a higher FFMI (0.07 SDS per 1 point higher diet quality, 95%CI: 0.05,0.10), and not FMI. For bone health, we observed associations of higher diet quality with higher BMD (0.05 SDS, 95%CI: 0.03,0.08) and BMC (0.06 SDS, 95%CI: 0.03,0.09), but not with aBMC. These associations were independent of diet quality in infancy and not driven by specific food components included in the diet quality score. ConclusionsIn this healthy population of children in Europe, we observed a high prevalence of overweight, whereas overall diet quality of the children was suboptimal. Our findings emphasize that an adequate diet in childhood is of high importance, not only for body composition, but also for bone health already at this young age. Dietary intake according to dietary guidelines in childhood may have a beneficial effect on growth and bone development, and may decrease the risk of obesity and osteoporosis later in life. Funding SourcesThis specific project did not receive any funding.

Scaling of adult human bone and skeletal muscle mass to height in the US population.

The scaling of structural components to body size is well studied in mammals, although comparable human observations in a large and diverse sample are lacking. The current study aimed to fill this gap by examining the scaling relationships between total body (TB) and regional bone and skeletal muscle (SM) mass with body size, as defined by stature, in a nationally representative sample of the US population. Subjects were 17,126 non-Hispanic (NH) white, NH black, and Mexican American men and women, aged ≥18 years, evaluated in the National Health and Nutrition Examination Survey who had TB and regional bone mineral (BMin) and lean soft tissue (LST) mass measured by dual-energy X-ray absorptiometry. BMin and appendicular LST served as surrogate bone and SM mass measures, respectively. The allometric model, BMin or LST = α(height)β , in a logarithmic form was used to generate scaling exponents. The findings were similar across all gender and race groups: body mass scaled to height with powers of ~2.0 (mean β ± SE, 1.94 ± 0.08-2.29 ± 0.09) while TB and appendicular BMin and appendicular LST scaled to height with consistently larger powers than those for body mass (eg, all P < .05 in NH white men and women); the largest BMin and LST scaling powers to height were observed in the lower extremities. Bone and SM mass, notably those of the lower extremities, increase as proportions of body mass with greater adult height. Metabolic and biomechanical implications emerge from these observations, the first of their kind in a representative adult US population sample.

Effect of esculetin on bone metabolism in ovariectomized rats

OBJECTIVETo determine the effect of an esculetin formulation (at 97.4% purity) on osteoporosis, and to investigate the potential underlying molecular mechanism(s). METHODSSixty specific pathogen free-grade female Wistar rats were randomly assigned to three groups: blank control (n = 12), sham (n = 12), and model (n = 36). The model group were bilaterally ovariectomized. The sham group had the tissue surrounding the ovaries removed, while the ovaries were retained. After 3 months, the model group was randomly divided into three subgroups: OVX (n = 12), positive control (n = 12), and esculetin (n = 12). The positive control group and the esculetin group were intragastrically administered diethylstilbestrol (0.046 mg • kg−1 • d−1) or esculetin (384 mg • kg−1 • d−1), respectively, once per day for 6 consecutive days; medication administration was then stopped for 1 d, before being administered for another 6 consecutive days. All rats were treated for 3 months. Samples were collected at the end of the treatment period. An Osteocore3 Digital 2D bone densitometer was used to test the bone mineral density, and histomorphometric analysis was performed to measure bone mass, bone formation, and bone resorption. Enzyme-linked immunosorbent assay analysis was used to measure the serum concentrations of interleukin-6 (IL-6), osteoprotegerin (OPG), and receptor activator of nuclear factor-kappa B ligand (RANKL). Immunohistochemistry and in situ hybridization were performed to detect the protein and mRNA expressions of OPG and RANKL in osteoblasts and bone marrow stromal cells. RESULTSCompared with the OVX group, the esculetin group had significantly greater femoral bone mineral density and tibial trabecular bone volume, and significantly smaller trabecular resorption surface. The percentage of trabecular formation surface, average osteoid width, trabecular bone mineralization rate, and cortical bone mineralization rate did not significantly differ between groups. Compared with the sham group, the esculetin group had significantly decreased serum levels of IL-6 and RANKL, and significant downregulation of RANKL protein and mRNA expression levels in osteoblasts and bone marrow stromal cells; however, there was no significant difference between groups in OPG. CONCLUSIONEsculetin can increase bone mass by upregulating RANKL expression in osteoblasts and bone marrow stromal cells, and decreasing serum IL-6 concentration. This indicates that the therapeutic effect of esculetin on osteoporosis occurs via decreased bone resorption.

Overexpression of WNT16 Does Not Prevent Cortical Bone Loss Due to Glucocorticoid Treatment in Mice.

ABSTRACTGlucocorticoids (GC) are commonly used for the treatment of a wide variety of autoimmune, pulmonary, gastrointestinal, and malignancy conditions. One of the devastating side effects of GC use is osteoporotic fractures, particularly in the spine and hip. Bisphosphonates (BP) are the most commonly prescribed pharmacological agents for the prevention and treatment of GC‐induced osteoporosis (GIO). However, GIO is marked by reduced bone formation and BP serves mainly to decrease bone resorption. The WNT signaling pathway plays a major role in bone and mineral homeostasis. Previously, we demonstrated that overexpression of WNT16 in mice led to higher bone mineral density and improved bone microarchitecture and strength. We hypothesized that WNT16 overexpression would prevent bone loss due to glucocorticoid treatment in mice. To test our hypothesis, we treated adult wild‐type and WNT16‐transgenic mice with vehicle and GC (prednisolone; 2.1 mg/kg body weight) via slow‐release pellets for 28 days. We measured bone mass and microarchitecture by dual‐energy X‐ray absorptiometry (DXA) and micro‐CT, and performed gene expression and serum biochemical analysis. We found that GC treatment compared with the vehicle significantly decreased femoral areal bone mineral density (aBMD), bone mineral content (BMC), and cortical bone area and thickness in both wild‐type and transgenic female mice. In contrast, the trabecular bone parameters at distal femur were not significantly changed by GC treatment in male and female mice for both genotypes. Further, we observed significantly lower level of serum P1NP and a tendency of higher level of serum TRAP in wild‐type and transgenic mice due to GC treatment in both sexes. Gene expression analysis showed lower mRNA levels of Wnt16, Opg, and Opg/Rankl ratio in GC‐treated female mice for both genotypes compared with the sex‐matched vehicle‐treated mice. These data suggest that although WNT16 overexpression resulted in higher baseline bone mineral density and bone volume per trabecular volume (BV/TV) in the transgenic mice, this was insufficient to prevent bone loss in mice due to glucocorticoid treatment. © 2018 The Authors JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

The Influence of Body Size and Bone Mass on Cortical Bone Histomorphometry in Human Ribs

This study examines the influence of human adult body size and bone mass on cortical bone histomorphometry, and explores microstructural variation in mid-thoracic ribs. The sample consists of 213 individuals (n female = 82, n male = 131, mean age-at-death = 47.96 ± 15.71 years) from the Kirsten Skeletal Collection, Stellenbosch University, South Africa. Maximum femur length and femur maximum head diameter are used as proxies for height and weight; total cross-sectional area, endosteal area, and cortical area are used to derive measures of bone mass. Histomorphometric variables include osteon population density (OPD) and osteon area (On.Ar). Partial correlations, controlling for age, test for significant relationships among variables. A hierarchical regression model is used to determine unique variable contributions to On.Ar and OPD. Body size measurements do not correlate with either bone mass or histomorphometric variables, suggesting that size-standardization may not be necessary in studies of rib bone microstructure. Age is the most significant factor affecting OPD, while OPD is the best predictor of On.Ar. These findings suggest that age-related secondary osteon crowding affects osteon geometry. Understanding the biological mechanisms that direct bone remodeling and determine microstructural variation is essential for interpreting histological data. Anat Rec, 301:1788-1796, 2018. © 2018 Wiley Periodicals, Inc.

Wednesday, September 26, 2018 7:35 AM–9:00 AM ePosters: P5. Effect of glucocorticoid withdrawal on glucocorticoid-inducing bone impairment

BACKGROUND CONTEXT Glucocorticoid (GC) withdrawal after a short-term use was common in clinical practice like immediate post-transplant period. However, previous studies without setting age-control group failed to determine whether the BMD recovery was sufficient and whether it is necessary to accept anti-osteoporosis therapy after GC withdrawal. PURPOSE The aim of this study was to investigate the effect of GC withdrawal on bone impairment in glucocorticoid-induced osteoporosis (GIOP) rats. STUDY DESIGN/SETTING Twenty-four female Sprague-Dawley rats (3 months’ old) were randomly divided into two treatment groups: an untreated age-control group (con, n=12); another group receiving a dexamethasone injection (DEXA, n=12). Animals in the con group were euthanized at 3rd month (M3) and 6th month (M6), respectively. Six rats in the DEXA group were euthanized at 3rd month (M3), whereas GC intervention was withdrew in the remaining animals of DEXA group, which were euthanized at the end of 6th month (M6). OUTCOME MEASURES Bone mass, bone microarchitecture, biomechanical properties of vertebrae, morphology, serum levels of PINP and β-CTX were evaluated. METHODS Twenty-four female Sprague-Dawley rats (3 months’ old) were randomly divided into two treatment groups: an untreated age-control group (con, n=12); another group receiving a dexamethasone injection (DEXA, n=12). Animals in the con group were euthanized at 3rd month (M3) and 6th month (M6), respectively. Six rats in the DEXA group were euthanized at 3rd month (M3), whereas GC intervention was withdrew in the remaining animals of DEXA group, which were euthanized at the end of 6th month (M6). Bone mass, bone microarchitecture, biomechanical properties of vertebrae, morphology, serum levels of PINP and β-CTX were evaluated. RESULTS Compared with the con (M3) group, the con (M6) group showed significantly better bone quantity, morphology and quality. Compared with the con (M3) group, the DEXA (M3) group showed significantly lower BMC, BMD, BS/TV, BV/TV, Tb.N, Tb.Th, vBMD, bone strength, compressive displacement, energy absorption capacity, PINP levels, β-CTX levels, and damaged trabecular morphology. And the same change trend was observed in the comparison between the con (M6) group and DEXA (M6) group. Compared with the DEXA (M3) group, the DEXA (M6) group showed significantly higher BMC, BMD and AREA, but no significant difference in BS/TV, BV/TV, SMI, Tb.N, Tb.Th, Tb.Sp, vBMD, bone strength, bone stiffness, compressive displacement, energy absorption capacity, PINP levels, β-CTX levels, and improvement in trabecular morphology was observed. CONCLUSIONS These results indicate that the reverse effect of GC withdrawal for 3 months on bone impairment in GIOP rats was insufficient, which implied that related anti-osteoporosis treatment might be still necessitated after GC withdrawal in clinical setting.

Use of Breast Cancer Screening and Its Association with Later Use of Preventive Services among Medicare Beneficiaries.

Purpose To retrospectively assess whether there is an association between screening mammography and the use of a variety of preventive services in women who are enrolled in Medicare. Materials and Methods U.S. Medicare claims from 2010 to 2014 Research Identifiable Files were reviewed to retrospectively identify a group of women who underwent screening mammography and a control group without screening mammography in 2012. The screened group was divided into positive versus negative results at screening, and the positive subgroup was divided into false-positive and true-positive findings. Multivariate logistic regression models and inverse probability of treatment weighting were used to examine the relationship between screening status and the probabilities of undergoing Papanicolaou test, bone mass measurement, or influenza vaccination in the following 2 years. Results The cohort consisted of 555 705 patients, of whom 185 625 (33.4%) underwent mammography. After adjusting for patient demographics, comorbidities, geographic covariates, and baseline preventive care, women who underwent index screening mammography (with either positive or negative results) were more likely than unscreened women to later undergo Papanicolaou test (odds ratio [OR], 1.49; 95% confidence interval: 1.40, 1.58), bone mass measurement (OR, 1.70; 95% confidence interval: 1.63, 1.78), and influenza vaccine (OR, 1.45; 95% confidence interval: 1.37, 1.53). In women who had not undergone these preventive measures in the 2 years before screening mammography, use of these three services after false-positive findings at screening was no different than after true-negative findings at screening. Conclusion In beneficiaries of U.S. Medicare, use of screening mammography was associated with higher likelihood of adherence to other preventive guidelines, without a negative association between false-positive results and cervical cancer screening.

How Exercise and Dietary Intervention Affect the Outcome of Osteosarcopenic Obesity Syndrome?

Osteosarcopenic obesity (OSO) is described as the simultaneous presence of osteopenia/osteoporosis, sarcopenia, and increased adiposity. Over time, older adults with OSO syndrome might be at greater risk for loss of physical function and bone fractures. Furthermore, a sedentary lifestyle, inadequate nutrition, pharmaceutical drugs, and chronic conditions encompass the multifactorial nature of OSO syndrome. Physical activity and a healthy diet play a crucial role in management and treatment of OSO syndrome. Research has shown that even low-intensity physical activity or daily habitual activity can maintain bone mineral density, muscle strength, and improve muscle quality, and reduce adiposity. However, older adults with high risk of fall and injuries require tailored exercise intensity. Also, balanced daily intake of vitamin D, calcium, and protein is important in prevention and treatment of OSO syndrome in postmenopausal women. Effective measurement of bone mass, muscle mass, and strength is required when detecting OSO syndrome and to evaluate the balance, strength and endurance of elder individuals and severity of the condition.

The relationship of whole human vertebral body creep to geometric, microstructural, and material properties

Creep, the time dependent deformation of a structure under load, is an important viscoelastic property of bone and may play a role in the development of permanent deformity of the vertebrae in vivo leading to clinically observable spinal fractures. To date, creep properties and their relationship to geometric, microstructural, and material properties have not been described in isolated human vertebral bodies. In this study, a range of image-based measures of vertebral bone geometry, bone mass, microarchitecture and mineralization were examined in multiple regression models in an effort to understand their contribution to creep behavior. Several variables, such as measures of mineralization heterogeneity, average bone density, and connectivity density persistently appeared as significant effects in multiple regression models (adjusted r2: 0.17–0.56). Although further work is needed to identify additional tissue properties to fully describe the portion of variability not explained by these models, these data are expected to help understand mechanisms underlying creep and improve prediction of vertebral deformities that eventually progress to a clinically observable fracture.