Lower Bone Strength Research Articles

The Interaction of Voluntary Running Exercise and Food Restriction Induces Low Bone Strength and Low Bone Mineral Density in Young Female Rats.

There is a concern that the combination of exercise with food intake reduction has a risk of reducing bone strength and bone mass in young female athletes. We examined the influence of the interaction of voluntary running exercise and food restriction on bone in young female rats. Seven-week-old female Sprague-Dawley rats were divided into four groups: the sedentary and ad libitum feeding group (SED), voluntary running exercise and ad libitum feeding group (EX), sedentary and 30 % food restriction group (SED-FR), and voluntary running exercise and 30 % food restriction group (EX-FR). The experiment lasted 12 weeks. Statistical analysis was carried out by two-way analysis of variance with exercise and restriction as the between-subjects factors. As a result, there were significant interactions of running and restriction on energy availability, breaking force, breaking energy, and bone mineral density (BMD). Breaking force and energy in the EX group were significantly higher than in the SED group; breaking force and energy were significantly lower in the EX-FR group than in the EX group, and breaking force in the EX-FR group was significantly lower than that in the SED-FR group. BMD in the EX-FR group was significantly lower than in the EX and SED-FR groups. These results suggest that food restriction induced low bone strength in young female rats engaging in voluntary running exercise. Also, through the interaction of exercise and food restriction, voluntary running exercise combined food restriction, unlike ad libitum feeding conditions, induced low bone strength, and low BMD in young female rats.

Bone strength and muscle properties in postmenopausal women with and without a recent distal radius fracture.

Distal radius (wrist) fracture (DRF) in women over age 50 years is an early sign of bone fragility. Women with a recent DRF compared to women without DRF demonstrated lower bone strength, muscle density, and strength, but no difference in dual-energy x-ray absorptiometry (DXA) measures, suggesting DXA alone may not be a sufficient predictor for DRF risk. The objective of this study was to investigate differences in bone and muscle properties between women with and without a recent DRF. One hundred sixty-six postmenopausal women (50-78 years) were recruited. Participants were excluded if they had taken bone-altering medications in the past 6 months or had medical conditions that severely affected daily living or the upper extremity. Seventy-seven age-matched women with a fracture in the past 6-24 months (Fx, n = 32) and without fracture (NFx, n = 45) were measured for bone and muscle properties using the nondominant (NFx) or non-fractured limb (Fx). Peripheral quantitative computed tomography (pQCT) was used to estimate bone strength in compression (BSIc) at the distal radius and tibia, bone strength in torsion (SSIp) at the shaft sites, muscle density, and area at the forearm and lower leg. Areal bone mineral density at the ultradistal forearm, spine, and femoral neck was measured by DXA. Grip strength and the 30-s chair stand test were used as estimates of upper and lower extremity muscle strength. Limb-specific between-group differences were compared using multivariate analysis of variance (MANOVA). There was a significant group difference (p < 0.05) for the forearm and lower leg, with the Fx group demonstrating 16 and 19% lower BSIc, 3 and 6% lower muscle density, and 20 and 21% lower muscle strength at the upper and lower extremities, respectively. There were no differences between groups for DXA measures. Women with recent DRF had lower pQCT-derived estimated bone strength at the distal radius and tibia and lower muscle density and strength at both extremities.

Cystic fibrosis-related bone disease in children: Examination of peripheral quantitative computed tomography (pQCT) data

BackgroundThe investigation of skeletal health data beyond dual X-ray absorptiometry (DXA) is limited in young individuals with CF. We assessed volumetric bone mineral densities (BMD), and bone and muscle parameters using peripheral quantitative computed tomography (pQCT) in individuals with CF and controls, 7.00–17.99years. MethodsPeripheral QCT (XCT 3000, Stratec) measurements were made in 53 individuals with CF and 53 controls. Bone mineral content (BMC), total volumetric BMD (vBMD) and cross sectional area (CSA) of the bone were measured at the 4% and 66% sites of the non-dominant tibia and radius. Additionally, trabecular vBMD and bone strength index (BSIc) were measured at the 4% sites, and cortical vBMD, muscle CSA (mCSA) and strength strain index (SSI) were measured at the 66% sites. ResultsPre-pubertal males with CF had greater trabecular vBMD (p=0.01) and total vBMD (p=0.00) at 4% tibia, and greater total vBMD (p=0.02) at 4% radius. Pre-pubertal females with CF had greater total vBMD at 66% tibia (p=0.02) and radius (p=0.04), and cortical vBMD (p=0.04) at the radius. At puberty, the CF cohort had less BMC at 4% tibia (males, p=0.02; females, p=0.01), and smaller mCSA at 66% tibia (males, p=0.02; females, p=0.01). Pubertal CF females had a smaller bone CSA (p=0.01) at 4% tibia, and lower bone strength (SSI) at the tibia (p=0.00) and radius (p=0.05) sites. ConclusionsBone strength parameters were not compromised prior to puberty in this CF cohort. At puberty, the bone phenotype changed for this CF cohort, showing several deficits compared to the controls. However, bone strength was adapting to the mechanical demands of the muscle. Altered bone parameters and their implications for lowered bone strength with increased age may be greatly influenced by: the CF cohort remaining smaller for age and/or a reduced bone strain, secondary to reduced muscle force.

The muscle–bone interaction in Turner syndrome

ObjectivesTurner syndrome (TS) is associated with an increased fracture rate due to reduced bone strength, which is mainly determined by skeletal muscle force. This study aimed to assess the muscle force–bone strength relationship in TS and to compare it with that of healthy controls. MethodsThis study included 39 girls with TS and 67 healthy control girls. Maximum muscle force (Fmax) was assessed through multiple one-legged hopping with jumping mechanography. Peripheral quantitative computerized tomography assessed the bone strength index at the tibial metaphysis (BSI 4) and the polar strength–strain index at the diaphysis (SSI polar 66). The effect of TS on the muscle–bone unit was tested using multiple linear regression. ResultsTS had no impact on Fmax (p=0.14); however, a negative effect on bone strength (p<0.001 for BSI 4 and p<0.01 for SSI polar 66) was observed compared with healthy controls. Bone strength was lower in the TS group (by 18%, p<0.01, for BSI 4 and by 7%, p=0.027, for SSI polar 66), even after correcting for Fmax. ConclusionsSimilar muscle force induces lower bone strength in TS compared with healthy controls, which suggests altered bone-loading sensitivity in TS.

Adult bone strength of children from single-parent families: the Midlife in the United States Study.

Bone health may be negatively impacted by childhood socio-environmental circumstances. We examined the independent associations of single-parent childhood and parental death or divorce in childhood with adult bone strength indices. Longer exposure to a single-parent household in childhood was associated with lower bone strength in adulthood. Because peak bone mass is acquired during childhood, bone health may be negatively impacted by childhood socio-environmental disadvantage. The goal of this study was to determine whether being raised in a single-parent household is associated with lower bone strength in adulthood. Using dual-energy X-ray absorptiometry data from 708 participants (mean age 57 years) in the Midlife in the United States Biomarker Project, we examined the independent associations of composite indices of femoral neck bone strength relative to load (in three failure modes: compression, bending, and impact) in adulthood with the experience of single-parent childhood and parental death or divorce in childhood. After adjustment for gender, race, menopause transition stage, age, and body mass index, each additional year of single-parent childhood was associated with 0.02 to 0.03 SD lower indices of adult femoral neck strength. In those with 9-16 years of single-parent childhood, the compression strength index was 0.41 SD lower, bending strength index was 0.31 SD lower, and impact strength index was 0.25 SD lower (all p values < 0.05). In contrast, parental death or divorce during childhood was not by itself independently associated with adult bone strength indices. The magnitudes of these associations were unaltered by additional adjustment for lifestyle factors and socioeconomic status in childhood and adulthood. Independent of parental death or divorce, growing up in a single-parent household is associated with lower femoral neck bone strength in adulthood, and this association is not entirely explained by childhood or adult socioeconomic conditions or lifestyle choices.

High-resolution peripheral quantitative CT imaging: Cortical porosity, poor trabecular bone microarchitecture, and low bone strength in lung transplant recipients.

To characterize bone microarchitecture and quantify bone strength in lung transplant (LT) recipients by using high-resolution (HR) peripheral quantitative computed tomographic (CT) imaging of the ultradistal radius. After study approval by the local ethics committee, all participants provided written informed consent. Included were 118 participants (58 LT recipients [mean age, 46.8 years ± 1.9; 30 women, 28 men] and 60 control participants [mean age, 39.9 years ± 1.9; 41 women, 19 men]) between April 2010 and May 2012. HR peripheral quantitative CT of the ultradistal radius was performed and evaluated for bone mineral density and trabecular and cortical bone microarchitecture. Mechanical competence was quantified by microfinite element analysis. Differences between LT recipients and control participants were determined by using two-way factorial analysis of covariance with age adjustment. Total and trabecular bone mineral density were significantly lower (-13.4% and -16.4%, respectively; P = .001) in LT recipients than in healthy control participants. LT recipients had lower trabecular number (-9.7%; P = .004) and lower trabecular thickness (-8.1%; P = .025). Trabecular separation and trabecular network heterogeneity were higher (+24.3% and +63.9%, respectively; P = .007 and P = .012, respectively) in LT recipients. Moreover, there was pronounced cortical porosity (+31.3%; P = .035) and lower cortical thickness (-10.2%, P = .005) after LT. In addition, mechanical competence was impaired, which was reflected by low stiffness (-15.0%; P < .001), low failure force (-14.8%; P < .001), and low bone strength (-14.6%; P < .001). Men and women with recent LT showed severe deficits in cortical and trabecular bone microarchitecture. Poor bone microarchitecture and low bone strength are likely to contribute to high fracture susceptibility observed in LT recipients.

Higher glucocorticoid secretion in the physiological range is associated with lower bone strength at the proximal radius in healthy children: importance of protein intake adjustment.

Whether higher production of glucocorticoids (GCs) within the physiological range may already be affecting bone status in healthy children is unknown. Because dietary protein intake affects both bone and GCs, we examined the association of urinary measures of glucocorticoid status and cortical bone in healthy non-obese children, after particularly controlling for protein intake. Proximal forearm bone parameters were measured by peripheral quantitative computed tomography (pQCT). Subjects studied (n = 175, 87 males, aged 6 to 18 years) had two 24-hour urine samples collected: the first sample at 1 year before bone measurement, and the second sample at the time of bone measurement. Major urinary GC metabolites were measured by mass spectrometry and summed to assess daily adrenal GC secretion (∑C21). Urinary free cortisol (UFF) and cortisone (UFE) were summed to assess potentially bioactive free GCs (UFF + UFE). After controlling for several covariates and especially urinary nitrogen (the biomarker of protein intake) cortisol secretion ∑C21 was inversely associated with all analyzed pQCT measures of bone quality. ∑C21 also predicted a higher endosteal and lower periosteal circumference, explaining both a smaller cortical area and (together with lower BMD) a lower strength-strain-index (SSI). UFF + UFE, UFE itself, and a urinary metabolite-estimate of 11beta-hydroxysteroid dehydrogenase type1 (11beta-HSD1) activity showed corresponding reciprocal associations (p < 0.05) with BMD and bone mineral content, but not with SSI and bone geometry variables. In conclusion, higher GC levels, even within the physiological range, appear to exert negative influences on bone modeling and remodeling already during growth. Our physiological data also suggest a relevant role of cortisone as the direct source for intracrine-generated cortisol by bone cell 11beta-HSD1.

Time since onset of walking predicts tibial bone strength in early childhood

Bone strength in adulthood is known to be affected by health at birth and early childhood. Habitual bone loading is a primary determinant of bone strength in later childhood and adulthood. However, the effects of physical activity in early childhood (e.g. crawling, standing and walking) on bone strength are unknown. Fifty-three children (twenty-seven males) were included in a longitudinal study in their early infancy. Shortly after birth (0.3±0.3months), details of mass and height were obtained along with a pQCT scan at 20% distal–proximal tibia length. At 14.8±0.5months of age the same data were collected, along with details of age at onset of standing, crawling, supported and unsupported walking. Time since onset of walking unsupported was associated with greater bone mass, cortical bone area, pericortical circumference and polar moment of inertia of both total and cortical bone (all P<0.05). There were no significant associations between other physical activity timepoints and bone measures. Age at onset of walking was not significantly related to mass, length or bone measures at birth. The results suggest that time since attainment of independent walking — representing exposure of the tibia to the large reaction and muscular forces associated with locomotion — is a primary determinant of bone strength in early childhood. This finding raises the possible opportunity of physical activity interventions at young age in paediatric populations associated with low childhood bone strength and late walking (e.g. low birth weight, cerebral palsy and Down's Syndrome, etc.).

Additive effect of PTH (1–34) and zoledronate in the prevention of disuse osteopenia in rats

Immobilization is known to cause a rapid bone loss due to increased osteoclastic bone resorption and decreased osteoblastic bone formation. Zoledronate (Zln) is a potent anti-resorptive pharmaceutical, while intermittent PTH is a potent bone anabolic agent. The aim of the present study was to investigate whether PTH or Zln alone or in combination could prevent immobilization-induced osteopenia.Immobilization was achieved by injecting 4IU Botox (BTX) into the right hind limb musculature. Seventy-two 16-week-old female Wistar rats were randomized into 6 groups; baseline (Base), control (Ctrl), BTX, BTX+PTH, BTX+Zln, and BTX+PTH+Zln. PTH (1–34) (80μg/kg) was given 5days/week and Zln (100μg/kg) was given once at study start. The animals were killed after 4weeks of treatment. The bone properties were evaluated using DEXA, μCT, dynamic bone histomorphometry, and mechanical testing.BTX resulted in lower femoral trabecular bone volume fraction (BV/TV) (−25%, p<0.05), lower tibial trabecular bone formation rate (BFR/BS) (−29%, p<0.05), and lower bone strength (Fmax) at the distal femur (−19%, p<0.001) compared with Ctrl. BTX+PTH resulted in higher femoral BV/TV (+31%, p<0.05), higher tibial trabecular BFR/BS (+297%, p<0.05), and higher Fmax at the distal femur (+11%, p<0.05) compared with BTX. BTX+Zln resulted in higher femoral BV/TV (+36%, p<0.05), lower tibial trabecular BFR/BS (−93%, p<0.05), and higher Fmax at the distal femur (+10%, p<0.05) compared with BTX. BTX+PTH+Zln resulted in higher femoral BV/TV (+70%, p<0.001), higher tibial trabecular BFR/BS (+59%, p<0.05), and higher Fmax at the distal femur (+32%, p<0.001) compared with BTX.In conclusion, BTX-induced immobilization led to lower BV/TV, BFR/BS, and Fmax. In general, PTH or Zln alone prevented the BTX-induced osteopenia, whereas PTH and Zln given in combination not only prevented, but also increased BV/TV and BFR/BS, and maintained Fmax at the distal femoral metaphysis compared with Ctrl.

Effects of sequential osteoporosis treatments on trabecular bone in adult rats with low bone mass.

We used an osteopenic adult ovariectomized (OVX) rat model to evaluate various sequential treatments for osteoporosis, using FDA-approved agents with complementary tissue-level mechanisms of action. Sequential treatment for 3 months each with alendronate (Aln), followed by PTH, followed by resumption of Aln, created the highest trabecular bone mass, best microarchitecture, and highest bone strength. Individual agents used to treat human osteoporosis reduce fracture risk by ∼ 50-60%. As agents that act with complementary mechanisms are available, sequential therapies that mix antiresorptive and anabolic agents could improve fracture risk reduction, when compared with monotherapies. We evaluated bone mass, bone microarchitecture, and bone strength in adult OVX, osteopenic rats, during different sequences of vehicle (Veh), parathyroid hormone (PTH), Aln, or raloxifene (Ral) in three 90-day treatment periods, over 9 months. Differences among groups were evaluated. The interrelationships of bone mass and microarchitecture endpoints and their relationship to bone strength were studied. Estrogen deficiency caused bone loss. OVX rats treated with Aln monotherapy had significantly better bone mass, microarchitecture, and bone strength than untreated OVX rats. Rats treated with an Aln drug holiday had bone mass and microarchitecture similar to the Aln monotherapy group but with significantly lower bone strength. PTH-treated rats had markedly higher bone endpoints, but all were lost after PTH withdrawal without follow-up treatment. Rats treated with PTH followed by Aln had better bone endpoints than those treated with Aln monotherapy, PTH monotherapy, or an Aln holiday. Rats treated initially with Aln or Ral, then switched to PTH, also had better bone endpoints, than monotherapy treatment. Rats treated with Aln, then PTH, and returned to Aln had the highest values for all endpoints. Our data indicate that antiresorptive therapy can be coupled with an anabolic agent, to produce and maintain better bone mass, microarchitecture, and strength than can be achieved with any monotherapy.

Finite Element Analysis Applied to 3-T MR Imaging of Proximal Femur Microarchitecture: Lower Bone Strength in Patients with Fragility Fractures Compared with Control Subjects

To determine the feasibility of using finite element analysis applied to 3-T magnetic resonance (MR) images of proximal femur microarchitecture for detection of lower bone strength in subjects with fragility fractures compared with control subjects without fractures. This prospective study was institutional review board approved and HIPAA compliant. Written informed consent was obtained. Postmenopausal women with (n = 22) and without (n = 22) fragility fractures were matched for age and body mass index. All subjects underwent standard dual-energy x-ray absorptiometry. Images of proximal femur microarchitecture were obtained by using a high-spatial-resolution three-dimensional fast low-angle shot sequence at 3 T. Finite element analysis was applied to compute elastic modulus as a measure of strength in the femoral head and neck, Ward triangle, greater trochanter, and intertrochanteric region. The Mann-Whitney test was used to compare bone mineral density T scores and elastic moduli between the groups. The relationship (R(2)) between elastic moduli and bone mineral density T scores was assessed. Patients with fractures showed lower elastic modulus than did control subjects in all proximal femur regions (femoral head, 8.51-8.73 GPa vs 9.32-9.67 GPa; P = .04; femoral neck, 3.11-3.72 GPa vs 4.39-4.82 GPa; P = .04; Ward triangle, 1.85-2.21 GPa vs 3.98-4.13 GPa; P = .04; intertrochanteric region, 1.62-2.18 GPa vs 3.86-4.47 GPa; P = .006-.007; greater trochanter, 0.65-1.21 GPa vs 1.96-2.62 GPa; P = .01-.02), but no differences in bone mineral density T scores. There were weak relationships between elastic moduli and bone mineral density T scores in patients with fractures (R(2) = 0.25-0.31, P = .02-.04), but not in control subjects. CONCLUSION Finite element analysis applied to high-spatial-resolution 3-T MR images of proximal femur microarchitecture can allow detection of lower elastic modulus, a marker of bone strength, in subjects with fragility fractures compared with control subjects. MR assessment of proximal femur strength may provide information about bone quality that is not provided by dual-energy x-ray absorptiometry.

Maternal high fat feeding alters bone lipid content at weaning without long‐lasting effects on bone lipid content and bone strength in male offspring at young adulthood (1033.7)

High fat (HF) feeding after weaning results in elevated bone fatty acid content and reduced bone strength in growing rats and mice. However, the effect of a maternal HF diet to offspring in utero and during suckling is less characterized. Our study objective was to determine if maternal HF feeding altered male offspring bone lipid composition at weaning and 3 months of age, and if this was accompanied by lower bone strength. Female Wistar rats were fed either control (CON, 7% soybean oil by weight (TD.94045); n = 9) or HF (20% lard by weight (TD.02016); n = 9) diet for 10 weeks. Rats were bred and consumed their respective diets throughout pregnancy and lactation. All offspring were weaned to CON diet. At weaning, but not 3 months of age, percent mole fraction of polyunsaturated fatty acids were lower and monounsaturated fatty acids were higher in femur of offspring from dams fed HF diet than offspring of dams fed CON diet (P &lt;0.05). Peak load, the maximum force a bone withstands before fracture, was not different between groups at the femur (midpoint and neck) and 3rd lumbar vertebra at 3 months of age. In conclusion, in utero and suckling exposure to a HF diet does not have long‐lasting effects on bone health in this rat model. Moreover, at 3 months of age, lipid composition of femurs no longer reflects maternal HF feeding and may explain why bone strength is similar between groups.

Thyroid-stimulating hormone maintains bone mass and strength by suppressing osteoclast differentiation

It has been suggested that pituitary hormone might be associated with bone metabolism. To investigate the role of thyroid-stimulating hormone (TSH) in bone metabolism, we designed the present study as follows. After weaning, TSH receptor (TSHR) null mice (Tshr−/−) were randomly divided into a thyroxine treatment group (n=10) or non-treatment group (n=10); the treatment group received a dose of desiccated thyroid extract at 100ppm daily for 5 weeks. Age-matched wild-type (Tshr+/+, n=10) and heterozygote mice (Tshr+/−, n=10) served as controls. After 5 weeks, the animals were sacrificed, and the femurs were collected for histomorphometrical and biomechanical analyses. In addition, the effect of TSH on osteoclastogenesis was examined in the RAW264.7 osteoclast cell line. We found that compared with Tshr+/+ mice, Tshr−/− and Tshr+/− mice had lower bone strength. The histomorphometric results showed that trabecular bone volume, osteoid surface, osteoid thickness and osteoblast surface were significantly decreased, whereas the osteoclast surface was significantly increased in both Tshr−/− and Tshr+/− mice compared with Tshr+/+ mice. Bone resorption and formation in Tshr−/− mice were further enhanced by thyroxine replacement. bTSH inhibited osteoclast differentiation in vitro, as demonstrated by reduced development of TRAP-positive cells and down-regulation of differentiation markers, including tartrate-resistant acid phosphatase, matrix metallo-proteinase-9 and cathepsin K in RAW264.7 cells. Our results confirm that TSH increased bone volume and improved bone microarchitecture and strength at least partly by inhibiting osteoclastogenesis.

Multisystem Dysregulation and Bone Strength: Findings From the Study of Midlife in the United States

Accumulated dysregulation across multiple physiological systems, or allostatic load (AL), has been proposed as the biological pathway from psychosocial adversity to poor health. The objective of the study was to examine whether AL, constructed using biomarkers and medication data from seven systems (sympathetic, parasympathetic, hypothalamic-pituitary-adrenal axis, cardiovascular regulation, inflammation, and lipid and glucose metabolism), is associated with lower bone strength in a national sample. This was a cross-sectional study. Seven hundred three community-dwelling men and women from the Study of Midlife in the United States participated in the study. Bone mineral density (BMD) was measured in the femoral neck and lumbar spine. Femoral neck BMD was combined with bone size and body size to create composite indices of femoral neck strength relative to load in three failure modes: compression, bending, and impact. In mixed-effects linear regression controlling for clustering within families and adjusted for age, gender, race/ethnicity, body mass index, menopausal transition stage, childhood socioeconomic status, adult finances, education level, and study center, each SD increment in AL score was associated with between 0.10 and 0.11 SD decrements in lumbar spine BMD and each of the three composite strength indices (all values of P < .05). Gender modified the association of AL only with femoral neck BMD; each SD increment in AL score was associated with 0.21 SD decrement in femoral neck BMD in men (P < .01) but not in women. Accumulation of dysregulation across systems was modestly associated with lower bone strength. This study adds to the accumulating evidence that multisystem dysregulation, or AL, predicts a variety of adverse health outcomes.

Food restriction causes low bone strength and microarchitectural deterioration in exercised growing male rats.

The pathogenesis of bone disorders in young male athletes has not been well understood. We hypothesized that bone fragility is caused by low energy availability, due to insufficient food intake and excessive exercise energy expenditure in young male athletes. To examine this hypothesis, we investigated the influence of food restriction on bone strength and bone morphology in exercised growing male rats, using three-point bending test, dual-energy X-ray absormetry, and micro-computed tomography. Four-week-old male Sprague-Dawley rats were divided randomly into the following groups: the control (Con) group, exercise (Ex) group, food restriction (R) group, and food restriction plus exercise (REx) group after a 1-wk acclimatization period. Thirty-percent food restriction in the R and REx groups was carried out in comparison with that in the Con group. Voluntary running exercise was performed in the Ex and REx groups. The experimental period lasted 13 wk. At the endpoint of this experiment, the bone strength of the femurs and tibial BMD in the REx group were significantly lower than those in the Con group. Moreover, trabecular bone volume and cortical bone volume in the REx group were also significantly lower than those in the Con group. These findings indicate that food restriction causes low bone strength and microarchitectural deterioration in exercised growing male rats.

Bone properties of the humeral head and resistance to screw cutout.

Surgical treatment of fractures involving the proximal humeral head is hampered by complications. Screw cutout is the major pitfall seen in connection with rigid plating. We have exploited a bony explanation for this phenomenon.Materials and Methods:We examined the convex surface of the humeral head looking at the density and the topographical strength of the subchondral bone using mechanical testing of bone cylinders harvested from the humeral head. We also studied the osseous architecture of the subchondral bone and thickness of the boneplate of the humeral head using a 3-dimensional serial sectioning technique.Results:The bone strength and bone density correlated well and revealed large regional variations across the humeral head. Bone strength and stiffness of the trabecular bone came to a maximum in the most medial anterior and central parts of the humeral head, where strong textural anisotropy was also found. We found in particular a lower bone strength and density in the posterior and inferior regions of the humeral head. A rapid decline in bone strength within a few mm below a relatively thin subchondral plate was also reported.Clinical Relevance:We have in this paper explored some of the most important factors connected with screw stability at the cancellous bone level. We discovered large variations in bone density and bone strength across the joint surface rendering certain areas of the humeral head less suitable for screw placement. The use of rigid plate constructs with divergent screw directions will predictably place screws in areas of the humeral head comprising low density and low strength cancellous bone. New concepts of plates and plating techniques for the surgical treatment of complex fractures of the proximal humerus should take bone distribution, strength, and architecture into account.

Insulin Resistance and Bone Strength: Findings From the Study of Midlife in the United States

Although several studies have noted increased fracture risk in individuals with type 2 diabetes mellitus (T2DM), the pathophysiologic mechanisms underlying this association are not known. We hypothesize that insulin resistance (the key pathology in T2DM) negatively influences bone remodeling and leads to reduced bone strength. Data for this study came from 717 participants in the Biomarker Project of the Midlife in the United States Study (MIDUS II). The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated from fasting morning blood glucose and insulin levels. Projected 2D (areal) bone mineral density (BMD) was measured in the lumbar spine and left hip using dual-energy X-ray absorptiometry (DXA). Femoral neck axis length and width were measured from the hip DXA scans, and combined with BMD and body weight and height to create composite indices of femoral neck strength relative to load in three different failure modes: compression, bending, and impact. We used multiple linear regressions to examine the relationship between HOMA-IR and bone strength, adjusted for age, gender, race/ethnicity, menopausal transition stage (in women), and study site. Greater HOMA-IR was associated with lower values of all three composite indices of femoral neck strength relative to load, but was not associated with BMD in the femoral neck. Every doubling of HOMA-IR was associated with a 0.34 to 0.40 SD decrement in the strength indices (p<0.001). On their own, higher levels of fasting insulin (but not of glucose) were independently associated with lower bone strength. Our study confirms that greater insulin resistance is related to lower femoral neck strength relative to load. Further, we note that hyperinsulinemia, rather than hyperglycemia, underlies this relationship. Although cross-sectional associations do not prove causality, our findings do suggest that insulin resistance and in particular, hyperinsulinemia, may negatively affect bone strength relative to load.

Greater peak oxygen consumption is associated with lower bone strength in soldiers

In the military population even aerobically fit soldiers are at higher risk of stress fracture than their civilian counterparts. The purpose of this study was to determine the relationship between peak oxygen consumption (VO2) and bone strength in soldiers. Tibiae of 38 male soldiers (height 1.8 ±.08m (SD), mass 83.9 ±13.6kg, age 20.3 ±2. 9yr) were scanned using peripheral quantitative computed tomography at 38% and 66% of the length of the tibia. Bone strength (section modulus (Z) and stress strain index (SSI)) were calculated by Stratec XCT software. VO2 was measured via indirect spirometry. Pearson correlation analysis (sig., p ≤ 0.05) was used to explore relationships between VO2 (relative to body mass (BM) and lean body mass (LBM)) and bone strength. Mean VO2 was 53.4 ±0.9 ml·kg−1. Bone strength was positively correlated with BM, LBM, height, and limb length. Significant negative linear correlations between VO2 (adjusted for BM) and both SSI and Z were found at the 38% site (SSI, r = −0.42; Z, r = −0.400) and at the 66% site (SSI, r = −0.39; Z, r = −0.48). With VO2 normalized to LBM, these correlations became stronger at both the 38% site (SSI, r = −0.55; Z, r = −0.51; both p ≤ 0.001) and the 66% site (SSI, r = −0.56; Z, r = −0.58; both p &lt; 0.001). These data confirm that bone strength is correlated with anthropometric measures; however, the surprising finding was that bone strength was inversely related to peak VO2 in soldiers.

Reducing parathyroid hormone is essential for correcting cortical bone deficiencies associated with chronic kidney disease

Chronic kidney disease (CKD) results in an increased fracture risk, partially due to elevations in parathyroid hormone (PTH). Bisphosphonates (BP's) reduce fracture risk by preventing bone loss, but the lack of data in CKD has limited their use. Using the BP zoledronic acid (ZOL) and calcium (CA) (known to lower PTH), the present study used a rat model of CKD to examine the impact of PTH levels on the skeletal abnormalities associated with kidney disease. Skeletally mature male rats with CKD (n=56) were given vehicle, ZOL, CA, or ZOL&amp;CA for 10 weeks. Age‐matched male rats without CKD (n=14) served as controls. Outcomes were determined by serum PTH, femoral cortical porosity, and femoral mechanical testing. In untreated CKD animals, PTH levels were 12 times higher than in normal animals. Animals treated with CA and ZOL&amp;CA had lower PTH values, whereas rats with ZOL alone did not. Compared to normal animals, untreated CKD rats had 41‐fold higher cortical porosity and lower bone strength (−31%). After correcting for differences in porosity, reductions in strength remained (−27%), indicating that CKD adversely impacts bone quality. Animals treated with CA and ZOL&amp;CA had cortical porosity and bone strength similar to normal controls. ZOL alone did not alter porosity or strength relative to untreated CKD rats. These data indicate that normalization of PTH is necessary for controlling cortical bone abnormalities in CKD.Grant Funding Source: NIH

Intensive glycemic control and thiazolidinedione use: effects on cortical and trabecular bone at the radius and tibia.

Factors that contribute to bone fragility in type 2 diabetes are not well understood. We assessed the effects of intensive glycemic control, thiazolidinediones (TZDs), and A1C levels on bone geometry and strength at the radius and tibia. In a substudy of the Action to Control Cardiovascular Risk in Diabetes trial, peripheral quantitative computed tomographic (pQCT) scans of the radius and tibia were obtained 2 years after randomization on 73 participants (intensive n = 35, standard n = 38). TZD use and A1C levels were measured every 4 months during the trial. Effects of intervention assignment, TZD use, and A1C on pQCT parameters were assessed in linear regression models. Intensive, compared with standard, glycemic control was associated with 1.3 % lower cortical volumetric BMD at the tibia in men (p = 0.02) but not with other pQCT parameters. In women, but not men, each additional year of TZD use was associated with an 11 % lower polar strength strain index (SSIp) at the radius (p = 0.04) and tibia (p = 0.002) in models adjusted for A1C levels. In women, each additional 1 % increase in A1C was associated with an 18 % lower SSIp at the ultradistal radius (p = 0.04) in models adjusted for TZD use. There was no consistent evidence of an effect of intensive, compared with standard, glycemic control on bone strength at the radius or tibia. In women, TZD use may reduce bone strength at these sites. Higher A1C may also be associated with lower bone strength at the radius, but not tibia, in women.