Site-specific,adult bone benefits attributed to loading during youth: A preliminary longitudinal analysis

We examined site-specific bone development in relation to childhood and adolescent artistic gymnastics exposure, comparing up to 10 years of prospectively acquired longitudinal data in 44 subjects, including 31 non-gymnasts (NON) and 13 gymnasts (GYM) who participated in gymnastics from pre-menarche to ≥ 1.9 years post-menarche. Subjects underwent annual regional and whole-body DXA scans; indices of bone geometry and strength were calculated. Anthropometrics, physical activity, and maturity were assessed annually, coincident with DXA scans. Non-linear mixed effect models centered growth in bone outcomes at menarche and adjusted for menarcheal age, height, and non-bone fat-free mass to evaluate GYM-NON differences. A POST-QUIT variable assessed the withdrawal effect of quitting gymnastics. Curves for bone area, mass (BMC), and strength indices were higher in GYM than NON at both distal radius metaphysis and diaphysis (p < 0.0001). At the femoral neck, greater GYM BMC (p < 0.01), narrower GYM endosteal diameter (p < 0.02), and similar periosteal width (p = 0.09) yielded GYM advantages in narrow neck cortical thickness and buckling ratio (both p < 0.001; lower BR indicates lower fracture risk). Lumbar spine and sub-head BMC were greater in GYM than NON (p < 0.036). Following gymnastics cessation, GYM slopes increased for distal radius diaphysis parameters (p ≤ 0.01) and for narrow neck BR (p = 0.02). At the distal radius metaphysis, GYM BMC and compressive strength slopes decreased, as did slopes for lumbar spine BMC, femoral neck BMC, and narrow neck cortical thickness (p < 0.02). In conclusion, advantages in bone mass, geometry, and strength at multiple skeletal sites were noted across growth and into young adulthood in girls who participated in gymnastics loading to at least 1.9 years post-menarche. Following gymnastics cessation, advantages at cortical bone sites improved or stabilized, while advantages at corticocancellous sites stabilized or diminished. Additional longitudinal observation is necessary to determine whether residual loading benefits enhance lifelong skeletal strength.     

Evaluating the relationship between muscle and bone modeling response in older adults

Bone modeling, the process that continually adjusts bone strength in response to prevalent muscle-loading forces throughout an individual's lifespan, may play an important role in bone fragility with age. Femoral stress, an index of bone modeling response, can be estimated using measurements of DXA derived bone geometry and loading information incorporated into an engineering model. Assuming that individuals have adapted to habitual muscle loading forces, greater stresses indicate a diminished response and a weaker bone. The purpose of this paper was to evaluate the associations of lean mass and muscle strength with the femoral stress measure generated from the engineering model and to examine the extent to which lean mass and muscle strength account for variation in femoral stress among 2539 healthy older adults participating in the Health ABC study using linear regression. Mean femoral stress was higher in women (9.51, SD = 1.85 Mpa) than in men (8.02, SD = 1.43 Mpa). Percent lean mass explained more of the variation in femoral stress than did knee strength adjusted for body size (R² = 0.187 vs. 0.055 in men; R² = 0.237 vs. 0.095 in women). In models adjusted for potential confounders, for every percent increase in lean mass, mean femoral stress was 0.121 Mpa lower (95% CI: − 0.138, − 0.104; p < 0.001) in men and 0.139 Mpa lower (95% CI: − 0.158, − 0.121; p < 0.001) in women. The inverse association of femoral stress with lean mass and with knee strength did not differ by category of BMI. Results from this study provide insight into bone modeling differences as measured by femoral stress among older men and women and indicate that lean mass may capture elements of bone's response to load.     

Location of atypical femoral fracture can be determined by tensile stress distribution influenced by femoral bowing and neck-shaft angle: a CT-based nonlinear finite element analysis model for the assessment of femoral shaft loading stress

IntroductionLoading stress due to individual variations in femoral morphology is thought to be strongly associated with the pathogenesis of atypical femoral fracture (AFF). In Japan, studies on AFF regarding pathogenesis in the mid-shaft are well-documented and a key factor in the injury is thought to be femoral shaft bowing deformity. Thus, we developed a CT-based finite element analysis (CT/FEA) model to assess distribution of loading stress in the femoral shaft.Patients and MethodsA multicenter prospective study was performed at 12 hospitals in Japan from August 2015 to February 2017. We assembled three study groups—the mid-shaft AFF group (n = 12), the subtrochanteric AFF group (n = 10), and the control group (n = 11)—and analyzed femoral morphology and loading stress in the femoral shaft by nonlinear CT/FEA.ResultsFemoral bowing in the mid-shaft AFF group was significantly greater (lateral bowing, p < 0.0001; anterior bowing, p < 0.01). Femoral neck-shaft angle in the subtrochanteric AFF group was significantly smaller (p < 0.001). On CT/FEA, both the mid-shaft and subtrochanteric AFF group showed maximum tensile stress located adjacent to the fracture site. Quantitatively, there was a correlation between femoral bowing and the ratio of tensile stress, which was calculated between the mid-shaft and subtrochanteric region (lateral bowing, r = 0.6373, p < 0.0001; anterior bowing, r = −0.5825, p < 0.001).ConclusionsCT/FEA demonstrated that tensile stress by loading stress can cause AFF. The location of AFF injury could be determined by individual stress distribution influenced by femoral bowing and neck-shaft angle.     

Measurement of Bone Density Around the Oxford Medial Compartment Knee Replacement Using iDXA. A Precision Study

The goal of this study was to evaluate whether the Lunar iDXA densitometer can accurately measure the bone mineral density (BMD) around the tibial component of the Oxford unicompartment knee replacement (UKR). Both knees in 20 patients were measured 3 times in the supine position with repositioning between each scan. We chose 7 regions of interest to evaluate the bone density around the implant. Small but significant differences between the implant and nonimplanted knee were noticed with the nonimplanted knee having slightly higher BMD and bone mineral content (BMC) in areas 1–3 (p ≤ 0.001) and area 6 (p = 0.002). There was higher BMD in area 4 (p = 0.028). The precision for BMD in the 7 areas of interest in the implanted knee varied between 0.55% and 4.04% and BMC between 1.8% and 5.3%. There was no significant difference in the precision between the nonimplanted and implanted knees. Prospective serial measurements around the Oxford UKR using iDXA will be able to assess specific areas of stress shielding and potential implant stability, which is likely to help predict the survival of the implant.     

Microcrack density and nanomechanical properties in the subchondral region of the immature piglet femoral head following ischemic osteonecrosis

Development of a subchondral fracture is one of the earliest signs of structural failure of the immature femoral head following ischemic osteonecrosis, and this eventually leads to a flattening deformity of the femoral head. The mechanical and mineralization changes in the femoral head preceding subchondral fracture have not been elucidated. We hypothesized that ischemic osteonecrosis leads to early material and mechanical alterations in the bone of the subchondral region. The purpose of this investigation was to assess the bone of the subchondral region for changes in the histology of bone cells, microcrack density, mineral content, and nanoindentation properties at an early stage of ischemic osteonecrosis in a piglet model. This large animal model has been shown to develop a subchondral fracture and femoral head deformity resembling juvenile femoral head osteonecrosis. The unoperated, left femoral head of each piglet (n = 8) was used as a normal control, while the right side had a surgical ischemia induced by disrupting the femoral neck vessels with a ligature. Hematoxylin and eosin (H&E) staining and TUNEL assay were performed on femoral heads from 3 piglets. Quantitative backscattered electron imaging, nanoindentation, and microcrack assessments were performed on the subchondral region of both control and ischemic femoral heads from 5 piglets. H&E staining and TUNEL assay showed extensive cell death and an absence of osteoblasts in the ischemic side compared to the normal control. Microcrack density in the ischemic side (3.2 ± 0.79 cracks/mm²) was significantly higher compared to the normal side (0.27 ± 0.27 cracks/mm²) in the subchondral region (p < 0.05). The weighted mean of the weight percent distribution of calcium (CaMean) also was significantly higher in the ischemic subchondral region (p < 0.05). Furthermore, the nanoindentation modulus within localized areas of subchondral bone was significantly increased in the ischemic side (16.8 ± 2.7 GPa) compared to the normal control (13.3 ± 3.2 GPa) (p < 0.05). Taken together, these results support the hypothesis that the nanoindentation modulus of the subchondral trabecular bone is increased in the early stage of ischemic osteonecrosis of the immature femoral head and makes it more susceptible to microcrack formation. We postulate that continued loading of the hip joint when there is a lack of bone cells to repair the microcracks due to ischemic osteonecrosis leads to microcrack accumulation and subsequent subchondral fracture.     

Phalangeal Quantitative Ultrasound and Bone Mineral Density in Evaluating Cortical Bone Loss: A Study in Postmenopausal Women With Primary Hyperparathyroidism and Subclinical Iatrogenic Hyperthyroidism

Twenty-five postmenopausal women with primary hyperparathyroidism (PHPT) and 30 age-matched women with subclinical hyperthyroidism (sHTH) were studied to assess cortical bone loss. One hundred two healthy women were also recruited. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry at lumbar spine (LS), femoral neck (FN) and femoral total (FT), and at one-third of the radius (R). Amplitude-dependent speed of sound (ADSoS) and Ultrasound Bone Profile Index (UBPI) were also evaluated using phalangeal quantitative ultrasound (QUS). A significant correlation was found between QUS and BMD at LS (ADSoS, p < 0.05) and R (ADSoS and UBPI, p < 0.001) in controls. QUS significantly correlated with BMD at LS, FN (p < 0.01), and FT (p < 0.001) in sHTH. No correlations were found in the PHPT group. Mean T-score values of all parameters were significantly lower in patients compared with controls (p < 0.001); however, they did not differ between PHPT and sHTH patients. T-score of R, ADSoS, and UBPI was reduced compared with other sites (p < 0.001) in both diseases. In postmenopausal women with PHPT and sHTH, bone loss is mainly detectable at cortical level. However, qualitative and/or structural changes of bone could account for the lack of correlations between these 2 techniques at cortical sites.     

Bone mass and anthropometry in patients with osteoarthritis of the foot and ankle

BackgroundPatients with hip and knee osteoarthritis (OA) have high bone mineral density (BMD) and high BMI. If the same accounts for patients with foot or ankle OA is unknown.MethodsWe measured BMD and femoral neck (FN) width by dual-energy X-ray absorptiometry in 42 women and 19 men with idiopathic OA in the foot or ankle, and in 99 women and 82 men as controls.ResultsWomen with OA had significant higher BMI than controls. Women with OA had higher BMI-adjusted BMD (p < 0.01) and smaller BMI-adjusted FN width (p < 0.01) than controls. Men with OA had higher BMI adjusted-BMD (p < 0.05) and smaller BMI-adjusted FN width (p < 0.01) than controls.ConclusionPatients with OA in the foot or ankle have higher BMD and smaller bone size than being expected by their BMI. This phenotype may provide unfavourable forces across the joint and is hypothetically important for development of OA.     

Age and Sex Differences in Estimated Tibia Strength: Influence of Measurement Site

Variability in peripheral quantitative computed tomography (pQCT) measurement sites and outcome variables limit direct comparisons of results between studies. Furthermore, it is unclear what estimates of bone strength are most indicative of changes due to aging, disease, or interventions. The purpose of this study was to examine age and sex differences in estimates of tibia strength. An additional purpose of this study was to determine which tibia site or sites are most sensitive for detecting age and sex differences in tibia strength. Self-identifying Caucasian men (n = 55) and women (n = 59) aged 20–59 yr had their tibias measured with pQCT from 5% to 85% of limb length in 10% increments distal to proximal. Bone strength index, strength strain index (SSI), moments of inertia (I_p, I_max, and I_min), and strength-to-mass ratios (polar moment of inertia to total bone mineral content [BMC] ratio [I_p:Tot.BMC] and strength strain index to total BMC ratio [SSI:Tot.BMC]) were quantified. There were significant (p < 0.01) site effects for all strength variables and strength-to-mass ratios. Site × sex interaction effects were significant (p < 0.05) for all strength variables. Men had greater (p < 0.01) values than women for all strength variables. Sex differences in I_p, I_max, I_p:Tot.BMC, SSI, and SSI:Tot.BMC ratios were the smallest at the 15% site and peaked at various sites, depending on variable. Site × age interactions existed for I_max, I_p:Tot.BMC, and SSI:Tot.BMC. There were significant age effects, I_max, I_p:Tot.BMC, and SSI:Tot.BMC, as values were the lowest in the 20–29 age group. Age and sex differences varied by measurement site and variable, and larger sex differences existed for moments of inertia than SSI. Strength-to-mass ratios may reflect efficiency of the whole bone architecture.     

Denosumab Densitometric Changes Assessed by Quantitative Computed Tomography at the Spine and Hip in Postmenopausal Women With Osteoporosis

FREEDOM was a phase 3 trial in 7808 women aged 60–90 yr with postmenopausal osteoporosis. Subjects received placebo or 60 mg denosumab subcutaneously every 6 mo for 3 yr in addition to daily calcium and vitamin D. Denosumab significantly decreased bone turnover; increased dual-energy X-ray absorptiometry (DXA) areal bone mineral density (aBMD); and significantly reduced new vertebral, nonvertebral, and hip fractures. In a subset of women (N = 209), lumbar spine, total hip, and femoral neck volumetric BMD (vBMD) were assessed by quantitative computed tomography at baseline and months 12, 24, and 36. Significant improvement from placebo and baseline was observed in aBMD and vBMD in the denosumab-treated subjects at all sites and time points measured. The vBMD difference from placebo reached 21.8%, 7.8%, and 5.9%, respectively, for the lumbar spine, total hip, and femoral neck at 36 mo (all p ≤ 0.0001). Compared with placebo and baseline, significant increases were also observed in bone mineral content (BMC) at the total hip (p < 0.0001) largely related to significant BMC improvement in the cortical compartment (p < 0.0001). These results supplement the data from DXA on the positive effect of denosumab on BMD in both the cortical and trabecular compartments.     

Effect of odanacatib on bone turnover markers,bone density and geometry of the spine and hip of ovariectomized monkeys: A head-to-head comparison with alendronate

Odanacatib (ODN) is a selective and reversible Cathepsin K (CatK) inhibitor currently being developed as a once weekly treatment for osteoporosis. Here, effects of ODN compared to alendronate (ALN) on bone turnover, DXA-based areal bone mineral density (aBMD), QCT-based volumetric BMD (vBMD) and geometric parameters were studied in ovariectomized (OVX) rhesus monkeys. Treatment was initiated 10 days after ovariectomy and continued for 20 months. The study consisted of four groups: L-ODN (2 mg/kg, daily p.o.), H-ODN (8/4 mg/kg daily p.o.), ALN (15 μg/kg, twice weekly, s.c.), and VEH (vehicle, daily, p.o.). L-ODN and ALN doses were selected to approximate the clinical exposures of the ODN 50-mg and ALN 70-mg once-weekly, respectively. L-ODN and ALN effectively reduced bone resorption markers uNTx and sCTx compared to VEH. There was no additional efficacy with these markers achieved with H-ODN. Conversely, ODN displayed inversely dose-dependent reduction of bone formation markers, sP1NP and sBSAP, and L-ODN reduced formation to a lesser degree than ALN. At month 18 post-OVX, L-ODN showed robust increases in lumbar spine aBMD (11.4%, p < 0.001), spine trabecular vBMD (13.7%, p < 0.001), femoral neck (FN) integral (int) vBMD (9.0%, p < 0.001) and sub-trochanteric proximal femur (SubTrPF) int vBMD, (6.4%, p < 0.001) compared to baseline. L-ODN significantly increased FN cortical thickness (Ct.Th) and cortical bone mineral content (Ct.BMC) by 22.5% (p < 0.001) and 21.8% (p < 0.001), respectively, and SubTrPF Ct.Th and Ct.BMC by 10.9% (p < 0.001) and 11.3% (p < 0.001) respectively. Compared to ALN, L-ODN significantly increased FN Ct. BMC by 8.7% (p < 0.05), and SubTrPF Ct.Th by 7.6% (p < 0.05) and Ct.BMC by 6.2% (p < 0.05). H-ODN showed no additional efficacy compared to L-ODN in OVX-monkeys in prevention mode. Taken together, the results from this study have demonstrated that administration of ODN at levels which approximate clinical exposure in OVX-monkeys had comparable efficacy to ALN in DXA-based aBMD and QCT-based vBMD. However, FN cortical mineral content clearly demonstrated superior efficacy of ODN versus ALN in this model of estrogen-deficient non-human primates.     

The effect of bone marrow mononuclear cells on vascularization and bone regeneration in steroid-induced osteonecrosis of the femoral head

ObjectiveWe examined whether implantation of autologous bone marrow mononuclear cells (BM-MNC) can augment neovascularization and bone regeneration in steroid-induced osteonecrosis of the femoral head.MethodsSixty-five 28-week-old male New Zealand white rabbits were divided into group I (left untreated, N = 20), group II (core decompression, N = 20) and group III (core decompression + autologous bone marrow cells implantation, N = 25) after receiving an established inductive protocol for inducing steroid-associated ON. Four weeks later, these rabbits were euthanized, bilateral femora were dissected for micro-CT-based microangiography to assess vascularization, and then the osteonecrotic changes and repair processes were examined histopathologically.ResultsQuantitative analysis showed that new vessel formation in group III was significantly greater compared with other groups at 4 weeks after treatment. Penetrating capillary vessels number vessels number in group III (44.5 ± 5.11) was significantly larger than that of group II (11.4 ± 2.46) and group I (3.10 ± 0.33) (p < 0.01). The histologic and histomorphometric analysis revealed that the new bone volume was significantly higher in the group III than in the group I and II, 4 weeks after treatment.ConclusionIn this animal model, a combination of bone marrow mononuclear cells and core decompression enhance the neovascularization and the osteoinductive ability, resulting in bone regeneration. These findings confirm the preliminary clinical results obtained in humans that the implantation of bone marrow mononuclear cells is an effective and feasible method for treating early osteonecrosis.     

Inverse association between bone microarchitecture assessed by HR-pQCT and coronary artery calcification in patients with end-stage renal disease

It is a matter of debate whether vascular calcification and bone loss are simultaneously occurring but largely independent processes or whether poor bone health predisposes to vascular calcification, especially in patients with kidney disease. Here we investigated the association between the changes of microarchitecture in weight bearing bone and the extent of coronary artery calcification in patients with chronic renal failure.The bone microarchitecture of the tibia using high-resolution peripheral quantitative computed tomography (HR-pQCT), bone mineral density using dual X-ray absorptiometry (DXA) of the lumbar spine, femoral neck and distal radius as well as coronary artery calcification using multi-slice CT and reported as Agatston score were measured in 66 patients with end-stage renal disease on chronic hemodialysis. Markers of bone turnover, vitamin D status and intact parathyroid hormone (iPTH) were assessed.CAC score was found to be < 100 in 39% and ≥ 100 in 61% of patients. The median [95% CI] total CAC score was 282 [315–2587]. By univariate analysis, significant correlations between CAC and age (R = 0.52, p < 0.001), weight (R = 0.3, p < 0.01) and serum cross laps (CTX, R = − 0.39, p < 0.01) were found, and parameters of bone microarchitecture were numerically but not significantly lower in patients with CAC scores ≥ 100. In multivariate analysis stratifying for gender and correcting for age, tibial density (D_tot) and bone volume/total volume (BV/TV) were significantly lower in patients with CAC scores ≥ 100 (p < 0.05 for both).Low trabecular bone volume and decreased cortical bone density are associated with coronary artery calcification in dialysis patients.     

Association Between Lean Mass and Handgrip Strength With Bone Mineral Density in Physically Active Postmenopausal Women

The present study evaluated 117 physically active postmenopausal women (67.8 ± 7.0 yr) who performed neuromotor physical tests (strength, balance, and mobility). Body composition (lean mass [g], fat mass [g], and % fat) and bone mineral density (BMD) of lumbar spine (L1–L4), femoral neck, and total body were measured by dual-energy X-ray absorptiometry. Following the World Health Organization criteria, osteoporosis was found in at least 1 analyzed site in 33 volunteers (28.2%): 30 (25.6%) in lumbar spine and 9 (7.7%) in femoral neck. Body weight was strongly and positively related to BMD in all sites, but the most important component of body composition was lean mass, also significantly related to all BMD sites, whereas fat mass was weakly related to the femoral neck BMD. Percent fat did not correlate with any BMD site. Of all the physical tests, the handgrip strength was most importantly related to lumbar spine, femoral neck, and total body (r = 0.49, p < 0.001; r = 0.56, p < 0.001; and r = 0.52, p < 0.001, respectively). The static body balance presented a weak but significant positive correlation only with lumbar spine. Our results suggest that strategies aiming to improve muscle strength and lean mass must contribute to the bone health of physically active postmenopausal women.     

Contribution of Fat-Free Mass and Fat Mass to Bone Mineral Density Among Reproductive-Aged Women of White,Black, and Hispanic Race/Ethnicity

The objective of the study was to evaluate the contribution of fat-free mass (FFM) and fat mass (FM) to bone mineral density (BMD) and bone mineral apparent density (BMAD) among reproductive-aged women. Dual-energy X-ray absorptiometry scans were performed on 708 healthy black, white, and Hispanic women, 16–33 yr of age. The independent effect of FFM and FM on BMD and BMAD and the interaction of body composition measurements with race/ethnicity and age, were evaluated. FFM correlated more strongly than FM with BMD at the lumbar spine (r = 0.52 vs r = 0.39, p < 0.01) and the femoral neck (r = 0.54 vs r = 0.41, p < 0.01). There was a significant positive association between bone density measures [ln(BMD) and ln(BMAD)] and both ln(FFM) and ln(FM). The association of FFM with spinal BMD was stronger in 16–24-yr-old women than in 25–33-yr-old women (p < 0.006). The effect of FFM on femoral neck BMD was greater in blacks (p < 0.043) than Hispanics, whereas the effect of FM on spinal BMD was less (p < 0.047). Both FM and FFM are important contributors to bone density although the balance of importance is slightly different between BMD and BMAD.     

Associations between amino acids and bone mineral density in men with idiopathic osteoporosis

Idiopathic osteoporosis in middle-aged men is characterized by low-level bone formation. Inhibited anabolism may be involved in the pathogenesis of the disease and amino acids may be of importance. In the present study fasting amino acid profiles in plasma and erythrocytes were determined in 22 male idiopathic osteoporosis (MIO) patients and in 20 age-matched healthy men and associated with bone mineral density, bone histomorphometry and hormones.The osteoporotic patients had normal plasma essential amino acids but increased non-essential amino acids (p = 0.001), particularly glutamine and glycine. The ratio essential/non-essential amino acids, an index of protein nutritional status, was decreased in the MIO patients (0.59 (0.04) μmol/l, mean (SD)), compared to controls (0.66 (0.05), p = 0.001).In the MIO patients, the ratio essential/non-essential plasma amino acids (r = 0.60, p = 0.003) was positively correlated with lumbar spine bone mineral density.The erythrocyte amino acids represent a large proportion of the free amino acids in blood. A novel finding was the lower levels of erythrocyte tryptophan in MIO (12 (2) μmol/l) compared to controls (16 (3), p = 0.001) and decreased erythrocyte/plasma ratio (0.28 (0.07) vs. 0.33, (0.06), p < 0.01), suggesting an altered amino acid transport of tryptophan between plasma and erythrocytes. In the combined group of MIO and control men (n = 42), bone mineral density was positively correlated with erythrocyte tryptophan in both the lumbar spine (r = 0.45, p = 0.003) and femoral neck (r = 0.56, p < 0.001). The bone histomorphometric variables wall thickness, trabecular thickness and mineral apposition rate were all positively associated with erythrocyte tryptophan levels in the MIO patients.In the combined group of MIO and controls, a multiple regression analysis showed that erythrocyte tryptophan could explain 22% of the variation of lumbar spine and 30% of the variation in femoral neck bone mineral density.We conclude that men with idiopathic osteoporosis have changes in free amino acid profiles which indicate their altered utilization. The correlations between tryptophan and bone mineral density and bone histomorphometry suggest a link between tryptophan and osteoblast function which may be important for bone health.     

Relationships of appendicular LMI and total body LMI to bone mass and physical activity levels in a birth cohort of New Zealand five-year olds

The present study was undertaken to determine whether children with lower bone mass display lower muscle mass for their height than those with high bone mineral content (BMC) and whether appendicular lean mass (bone-free lean mass in arms plus legs) is associated with physical activity and/or BMC in preschool children. 158 children (59% male) from a New Zealand cohort born in 2001–2002 were studied close to their fifth birthday. Body composition was measured by dual energy X-ray absorptiometry (Lunar DPX-L). Lean mass index (LMI) was calculated as lean mass (kg) divided by height in metres squared. Physical activity was assessed objectively by accelerometry (Actical Mini-Mitter). Girls and boys had similar heights, weights and daily accelerometry counts but boys had lower fat mass, and higher lean mass and total body BMC than the girls (P < 0.00l). In both sexes children with greater quantities of total and regional lean mass and higher LMI values had significantly higher bone mass. Appendicular LMI was more strongly associated with BMC than LMI. Accelerometry counts showed no associations with height but were positively associated with lean mass (r = 0.23, P < 0.03), appendicular LMI (r = 0.25 P < 0.01), total body BMC (r = 0.24, P < 0.02) and total body less head BMC (r = 0.27 P < 0.009) in the boys, but not in the girls. Greater time spent in more intense physical activity was also associated with higher appendicular lean mass and TBLH BMC only in the boys. We conclude that children with lower BMC values display not only lower lean mass but also lower total and appendicular lean mass for their height, than those with higher BMC values. The sex differences in associations of accelerometry counts to lean mass and BMC have been noted by others and require further investigation.     

The high bone mass phenotype is characterised by a combined cortical and trabecular bone phenotype: Findings from a pQCT case–control study

High bone mass (HBM), detected in 0.2% of DXA scans, is characterised by a mild skeletal dysplasia largely unexplained by known genetic mutations. We conducted the first systematic assessment of the skeletal phenotype in unexplained HBM using pQCT in our unique HBM population identified from screening routine UK NHS DXA scans.pQCT measurements from the mid and distal tibia and radius in 98 HBM cases were compared with (i) 65 family controls (constituting unaffected relatives and spouses), and (ii) 692 general population controls.HBM cases had substantially greater trabecular density at the distal tibia (340 [320, 359] mg/cm³), compared to both family (294 [276, 312]) and population controls (290 [281, 299]) (p < 0.001 for both, adjusted for age, gender, weight, height, alcohol, smoking, malignancy, menopause, steroid and estrogen replacement use). Similar results were obtained at the distal radius. Greater cortical bone mineral density (cBMD) was observed in HBM cases, both at the midtibia and radius (adjusted p < 0.001). Total bone area (TBA) was higher in HBM cases, at the distal and mid tibia and radius (adjusted p < 0.05 versus family controls), suggesting greater periosteal apposition. Cortical thickness was increased at the mid tibia and radius (adjusted p < 0.001), implying reduced endosteal expansion. Together, these changes resulted in greater predicted cortical strength (strength strain index [SSI]) in both tibia and radius (p < 0.001). We then examined relationships with age; tibial cBMD remained constant with increasing age amongst HBM cases (adjusted β ? 0.01 [? 0.02, 0.01], p = 0.41), but declined in family controls (? 0.05 [? 0.03, ? 0.07], p < 0.001) interaction p = 0.002; age-related changes in tibial trabecular BMD, CBA and SSI were also divergent. In contrast, at the radius HBM cases and controls showed parallel age-related declines in cBMD and trabecular BMD.HBM is characterised by increased trabecular BMD and by alterations in cortical bone density and structure, leading to substantial increments in predicted cortical bone strength. In contrast to the radius, neither trabecular nor cortical BMD declined with age in the tibia of HBM cases, suggesting attenuation of age-related bone loss in weight-bearing limbs contributes to the observed bone phenotype.     

Influences of age and mechanical stability on volume,microstructure, and mineralization of the fracture callus during bone healing: Is osteoclast activity the key to age-related impaired healing?

Earlier studies have shown that the influence of fixation stability on bone healing diminishes with advanced age. The goal of this study was to unravel the relationship between mechanical stimulus and age on callus competence at a tissue level. Using 3D in vitro micro-computed tomography derived metrics, 2D in vivo radiography, and histology, we investigated the influences of age and varying fixation stability on callus size, geometry, microstructure, composition, remodeling, and vascularity. Compared were four groups with a 1.5-mm osteotomy gap in the femora of Sprague–Dawley rats: Young rigid (YR), Young semirigid (YSR), Old rigid (OR), Old semirigid (OSR). Hypothesis was that calcified callus microstructure and composition is impaired due to the influence of advanced age, and these individuals would show a reduced response to fixation stabilities. Semirigid fixations resulted in a larger ΔCSA (Callus cross-sectional area) compared to rigid groups. In vitro µCT analysis at 6 weeks postmortem showed callus bridging scores in younger animals to be superior than their older counterparts (p < 0.01). Younger animals showed (i) larger callus strut thickness (p < 0.001), (ii) lower perforation in struts (p < 0.01), and (iii) higher mineralization of callus struts (p < 0.001). Callus mineralization was reduced in young animals with semirigid fracture fixation but remained unaffected in the aged group. While stability had an influence, age showed none on callus size and geometry of callus. With no differences observed in relative osteoid areas in the callus ROI, old as well as semirigid fixated animals showed a higher osteoclast count (p < 0.05). Blood vessel density was reduced in animals with semirigid fixation (p < 0.05). In conclusion, in vivo monitoring indicated delayed callus maturation in aged individuals. Callus bridging and callus competence (microstructure and mineralization) were impaired in individuals with an advanced age. This matched with increased bone resorption due to higher osteoclast numbers. Varying fixator configurations in older individuals did not alter the dominant effect of advanced age on callus tissue mineralization, unlike in their younger counterparts. Age-associated influences appeared independent from stability. This study illustrates the dominating role of osteoclastic activity in age-related impaired healing, while demonstrating the optimization of fixation parameters such as stiffness appeared to be less effective in influencing healing in aged individuals.     

iDXA,Prodigy, and DPXL Dual-Energy X-ray Absorptiometry Whole-Body Scans: A Cross-Calibration Study

PurposeTotal body fat, lean, and bone mineral content (BMC) in addition to regional fat and lean mass values for arms, legs, and trunk were compared across a pencil-beam (Lunar DPXL) and 2 fan-beam (GE Lunar Prodigy and GE Lunar iDXA) dual-energy X-ray absorptiometry (DXA) systems.MethodsSubjects were a multiethnic sample of 99 healthy adult males (47%) and females (mean ± SD: age, 46.3 ± 16.9 yr; weight, 73.4 ± 16.6 kg; height, 167.6 ± 9.7 cm; body mass index, 26.0 ± 5.2 kg/m²) who had whole-body scans performed within a 3-h period on the 3 systems. Repeated measures ANOVA was used to test the null hypothesis that the mean values for the 3 systems were equal. Translation equations between the methods were derived using regression techniques.ResultsBone mineral content (BMC): For both genders, total BMC by iDXA was lower (p ≤ 0.004) than the other systems. Lean: for males, iDXA was lower (p ≤ 0.03) than the other systems for total, trunk, and arms. For females, DPXL estimated higher (p < 0.001) lean mass compared with the other systems for total, trunk, and arms, but iDXA estimated greater legs lean mass. For both genders, all DPXL mean values were greater than Prodigy mean values (p < 0.001).Fat: in females, all the 3 systems were different from each other for total, trunk, and legs (p ≤ 0.04). For arms, DPXL and iDXA were higher than Prodigy (p < 0.0004). For males, DPXL was less (p < 0.001) for total body, trunk, and legs compared with the other 2 systems and greater than Prodigy only for arms (p < 0.0007). These data were used to derive translation equations between systems. For several measurements, the differences between systems were related to gender.ConclusionFor estimation of BMC and body composition, there was high agreement between all DXA systems (R² = 0.85–0.99). Even so, cross-calibration equations should be used to examine data across systems to avoid erroneous conclusions.