Cortical Bone Mineral Content Research Articles

Growth changes of the mandibular body with eruption of mandibular third molars: Analysis of anatomical morphometry and quantitative bone mineral content by using radiography

This study aimed to analyze growth changes in mandibular body morphology and quantitative bone mineral content (QBMC) with eruption of mandibular third molars (M3s) and the relationship between those variables and posterior mandibular body length. Linear and angular measurements were conducted using standard lateral radiographs of 37 dried mandibles in Hellman's dental developmental stages IVA (14 specimens) to VA (23 specimens). Cortical and trabecular basal bone mineral contents (CBMC and TBMC) in the mandible were expressed in millimeter titanium equivalent values using a titanium step wedge. The largest significant change in the mandibular body morphology was an increase in the horizontal dimension (M2DP'-Go': 7.59mm), followed by vertical dimension - total height of the mandibular body (THOMB: 4.96mm) and mandibular cortical width (MCW: 1.22mm). The gonial angle (GA) decreased significantly by 6.72° between stages IVA and VA. The mandibular cortical index (MCI) was classified only as C1 or C2 in each stage. Among 4 types of line profile, types 1 and 2 were most commonly observed in both stages. Mean values for CBMC and TBMC increased significantly between stages IVA and VA. Posterior mandibular body length (MeF'-Go') correlated positively with M2DP'-Go', THOM, MCW, and CBMC (r=0.816, 0.698, 0.595, and 0.507), respectively and negatively with GA (r=-0.582). These results demonstrated that the morphological changes in the posterior mandibular body and the QBMC increased significantly with M3 eruption, while the GA became significantly smaller. The posterior mandibular body length had a linear correlation with these variables.

Is breastfeeding related to bone properties? A longitudinal analysis of associations between breastfeeding duration and pQCT parameters in children and adolescents

Nutritive and bioactive components of human milk could be involved in programming metabolic systems that affect bone growth throughout the life course. Bone properties in childhood and adolescence might differ, depending on breastfeeding duration. Thus, breastfeeding could be a relevant factor in the context of primary osteoporosis prevention. The prospective association between breastfeeding duration and bone properties was investigated using the data of 284 participants of the Dortmund Nutritional and Anthropometric Longitudinally Designed Study. Breastfeeding duration was assessed during infancy. Bone properties were measured by peripheral quantitative computed tomography (pQCT) at ages 5-23 years. Cortical volumetric bone mineral density, cortical bone mineral content, strength strain index, total cross-sectional area of the bone and cross-sectional area of the cortical bone were determined at the 65% site of the radius. Linear regression analyses were performed to check for differences in pQCT parameters of subjects who had not or shortly been breastfed (0-16 weeks) and subjects who had been breastfed for a long duration (≥17 weeks). Multivariable models adjusted for age, gender, forearm length, muscle cross-sectional area, body mass index standard deviation score (SDS), height SDS and socio-economic status did not yield associations between breastfeeding duration and pQCT parameters. These findings suggest neither protective nor adverse effects of prolonged breastfeeding on bone health in childhood and adolescence. Influences of early nutrition on bone growth might be overridden by current effects of mechanical loads on bone physiology.

Site-Specific Variance in Radius and Tibia Bone Strength as Determined by Muscle Size and Body Mass

To investigate the predictive ability of muscle cross-sectional area (MCSA) and body mass on bone mineral content, compressive bone strength index (BSIc), and the polar stress-strain index (SSIp) of the forearms and lower legs of middle-aged adults. A total of 53 healthy adults (37 male, 16 female; mean age 50.4; SD 2.1 y) were scanned with peripheral quantitative computed tomography (pQCT) to measure radius and tibia total and cortical bone mineral content, BSIc, SSIp, and forearm and lower-leg MCSA (BSIc: 4% distal; SSIp and MCSA at 65% and 66% radius and tibia shaft sites, respectively). Multiple regression models adjusted for sex and height were used to assess the relative variance in radius or tibia bone outcomes predicted by body mass and/or forearm or lower-leg MCSA. Forearm MCSA independently predicted total bone-mineral content, BSIc, and SSIp in radius (r partial=0.59, 0.56, 0.42). Body mass was a negative predictor of radius BSIc (r partial=-0.32) and did not predict other radius outcomes when both body mass and MCSA were forced in the models. In the lower leg shaft, MCSA, and body mass predicted bone content and strength similarly when independently added to the models with sex and height. Forearm MCSA was a dominant predictor of radius bone content and estimated strength. In the tibia, both body mass and lower-leg MCSA contributed to predicting bone content and estimated strength.

Former premenarcheal gymnasts exhibit site-specific skeletal benefits in adulthood after long-term retirement

Young female gymnasts have greater bone strength compared to controls; although possibly due to selection into gymnastics, it is thought that their loading activity during growth increases their bone mass, influencing both bone geometry and architecture. If such bone mass and geometric adaptations are maintained, this may potentially decrease the risk of osteoporosis and risk of fracture later in life. However, there is limited evidence of the persisting benefit of gymnastic exercise during growth on adult bone geometric parameters. Therefore, the purpose of this study was to determine whether adult bone geometry, volumetric density, and estimated strength were greater in retired gymnasts compared to controls, 10 years after retirement from the sport. Bone geometric and densitometric parameters, measured by peripheral quantitative computed tomography (pQCT) at the radius and tibia, were compared between 25 retired female gymnasts and 22 controls, age range 22 to 30 years, by multivariate analysis of covariance (covariates: age, height, and muscle cross-sectional area). Retired gymnasts had significantly greater adjusted total and trabecular area (16%), total and trabecular bone mineral content (BMC) (18% and 22%, respectively), and estimated strength (21%) at the distal radius (p < 0.05) than controls. Adjusted total and cortical area and BMC, medullary area, and estimated strength were also significantly greater (13% to 46%) in retired gymnasts at the 30% and 65% radial shaft sites (p < 0.05). At the distal tibia, retired gymnasts had 12% to 13% greater total and trabecular BMC and volumetric bone mineral density as well as 21% greater estimated strength; total and cortical BMC and estimated strength were also greater at the tibial shaft (8%, 11%, and 10%, respectively) (p < 0.05). Former female gymnasts have significantly better geometric and densitometric properties, as well as estimated strength, at the radius and tibia 10 years after retirement from gymnastics compared to females who did not participate in gymnastics in childhood and adolescence.

Cortical and trabecular bone at the radius and tibia in male and female adolescents with Down syndrome: a peripheral quantitative computed tomography (pQCT) study

We aimed to describe the structure and strength of the tibia and radius of adolescents with Down syndrome. We observed that despite higher levels of volumetric bone mineral density in determined skeletal sites, they are at higher risk of developing osteoporotic fractures in the future due to their lower bone strength indexes. The aims of the study were to describe the cortical and trabecular volumetric bone mineral density (vBMD), bone mineral content (BMC), area, and bone strength in adolescents with Down syndrome (DS) and to compare them with adolescents without disabilities. Thirty adolescents (11 girls) with DS and 28 without disabilities (10 girls) participated in the study. Peripheral quantitative computed tomography measurements were taken at proximal and distal sites of the tibia and radius. Values of total, trabecular, and cortical BMC; vBMD; and area were obtained of each scan. Cortical thickness and endosteal and periosteal circumferences were also measured, and different bone strength indexes were calculated. Student's t tests were applied between groups. The DS group showed greater vBMD at distal radius, BMC at proximal radius, and total and cortical vBMD at proximal tibia. The non-DS group showed higher total and trabecular area at the distal radius and total, cortical, and trabecular BMC and area at distal tibia. Higher values of periosteal and endosteal circumference and bone strength were also found in non-DS group. From these results, it can be believed that even with higher vBMD in determined skeletal sites, adolescents with DS are at higher risk of suffering bone fractures due to an increased fragility by lower resistance to load bending or torsion.

Effect of Rheumatoid Arthritis on Volumetric Bone Mineral Density and Bone Geometry, Assessed by Peripheral Quantitative Computed Tomography in Postmenopausal Women Treated with Bisphosphonates

To investigate the effect of rheumatoid arthritis (RA) on volumetric bone mineral density (vBMD) and bone geometry in postmenopausal women treated with bisphosphonates. Fifty-three postmenopausal women with RA and 87 control subjects, comparable in terms of age, body mass index, and years since menopause, underwent peripheral quantitative computed tomography (pQCT) of the nondominant tibia. At 4% (trabecular site), trabecular bone mineral content (BMC) and vBMD (p < 0.001) were lower in the RA group, while trabecular area was comparable. At 38% (cortical site), cortical BMC (p < 0.01), area (p < 0.05), and thickness (p < 0.001) were lower in the RA group, whereas vBMD was comparable. Endosteal circumference was higher (p < 0.05), whereas periosteal circumference was comparable, indicating cancellization of cortical bone. In the RA group, muscle area was lower (p < 0.001), while at 14% polar stress strength index was significantly lower (p < 0.01) in patients with RA, indicating impairment of bone mechanical properties. RA is associated with negative effects on both cortical and cancellous bone in postmenopausal women treated with bisphosphonates. Cortical geometric properties are also adversely affected mainly by increased endosteal circumference, whereas trabecular geometric properties are generally preserved.

Assessment of dual-energy X-ray absorptiometry measures of bone health in pediatric chronic kidney disease.

Dual-energy X-ray absorptiometry (DXA) techniques are limited in childhood chronic kidney disease (CKD) by the confounding effect of short stature and opposing parathyroid hormone effects on trabecular and cortical bone. Peripheral quantitative computed tomography (pQCT) is not subject to these limitations. Lumbar spine (LS) and whole-body (WB) DXA and tibia pQCT scans were obtained in 88 stage 4-5 CKD and >650 healthy participants, ages 5-21 years. Sex- and race-specific Z-scores were generated for bone mineral density (BMD) and bone mineral content (BMC) by DXA, relative to age and adjusted for height Z-score (LS-BMD-Z and WB-BMC-Z), and compared to pQCT Z-scores for trabecular BMD (TrabBMD-Z) for age and cortical BMC (CortBMC-Z) for age and tibia length. LS-BMD-Z [0.50 (95% C.I. 0.28, 0.73), p<0.0001] and TrabBMD-Z [0.53 (0.27, 0.79), p<0.0001] were greater in CKD, and WB-BMC-Z [-0.36 (-0.53, -0.19), p<0.0001] and CortBMC-Z [-0.48 (-0.70, -0.27), p<0.0001] were lower, compared to reference participants. Z-scores were correlated at trabecular (LS-BMD-Z and TrabBMD-Z: R=0.36) and cortical (WB-BMC-Z and CortBMC-Z: R=0.64) sites in CKD; similar to correlations in reference participants. Lumbar spine and whole-body DXA suggested greater trabecular BMD and lower cortical BMC in CKD, consistent with pQCT results; however, correlations were modest. Studies are needed to identify methods that predict fracture in childhood CKD.

Long term higher urinary calcium excretion within the normal physiologic range predicts impaired bone status of the proximal radius in healthy children with higher potential renal acid load

Reduced bone mineral density (BMD) and bone mass have been observed in children with idiopathic hypercalciuria. Whether urinary calcium excretion at the higher end of the normal physiologic range can influence bone health in healthy children independent of dietary intake is unknown. Urinary calcium was quantified in 603 24-h urine samples from 154 healthy children and adolescents who had ≥3 urine collections and parallel 3-day weighed dietary records during the 4years preceding proximal forearm bone analyses by peripheral quantitative computed tomography (pQCT). Urinary potential renal acid load (uPRAL) was determined according to urine ionogram by subtracting measured quantitatively important mineral cations from nonbicarbonate anions. Urinary calcium excretion was significantly associated with volumetric (v)BMD (P=0.04), almost significantly with cortical bone mineral content (BMC) (P=0.05), but not with cortical cross-sectional area (CSA) (P=0.09), total CSA (P=0.3), or Strength-Strain Index (P=0.8) in the total population sample. Stratified analyses based on the median split of uPRAL showed that calcium excretion was negatively associated with vBMD (P=0.007), cortical BMC (P=0.001), and cortical CSA (P=0.004) in those children with higher uPRALs, but not in those with low uPRALs (P>0.3). In conclusion, long-term higher calciuria within the physiological range predicts reduced diaphyseal bone mass and bone density particularly in healthy children and adolescents with long-term unfavorable higher dietary acid load, i.e., with lower fruit and vegetable intake.

Site-specific advantages in skeletal geometry and strength at the proximal femur and forearm in young female gymnasts

PurposeWe evaluated site-specific skeletal adaptation to loading during growth, comparing radius (RAD) and femoral neck (FN) DXA scans in young female gymnasts (GYM) and non-gymnasts (NON). MethodsSubjects from an ongoing longitudinal study (8–26yr old) underwent annual DXA scans (proximal femur, forearm, total body) and anthropometry, completing maturity and physical activity questionnaires. This cross-sectional analysis used the most recent data meeting the following criteria: gynecological age ≤2.5yr post-menarche; and GYM annual mean gymnastic exposure ≥5.0h/wk in the prior year. Bone geometric and strength indices were derived from scans for 173 subjects (8–17yr old) via hip structural analysis (femoral narrow neck, NN) and similar radius formulae (1/3 and Ultradistal (UD)). Maturity was coded as M1 (Tanner I breast), M2 (pre-menarche, ≥Tanner II breast) or M3 (post-menarche). ANOVA and chi square compared descriptive data. Two factor ANCOVA adjusted for age, height, total body non-bone lean mass and percent body fat; significance was tested for main effects and interactions between gymnastic exposure and maturity. ResultsAt the distal radius, GYM means were significantly greater than NON means for all variables (p<0.05). At the proximal femur, GYM exhibited narrower periosteal and endosteal dimensions, but greater indices of cortical thickness, BMC, aBMD and section modulus, with lower buckling ratio (p<0.05). However, significant interactions between maturity and loading were detected for the following: 1) FN bone mineral content (BMC) and NN buckling ratio (GYM BMC advantages only in M1 and M3; for BMC and buckling ratio, M1 advantages were greatest); 2) 1/3 radius BMC, width, endosteal diameter, cortical cross-sectional area, and section modulus (GYM advantages primarily post-menarche); and 3) UD radius BMC and axial compressive strength (GYM advantages were larger with greater maturity, greatest post-menarche). ConclusionsMaturity-specific comparisons suggested site-specific skeletal adaptation to loading during growth, with greater advantages at the radius versus the proximal femur. At the radius, GYM advantages included greater bone width, cortical cross-sectional area and cortical thickness; in contrast, at the femoral neck, GYM bone tissue cross-sectional area and cortical thickness were greater, but bone width was narrower than in NON. Future longitudinal analyses will evaluate putative maturity-specific differences.

Changes in Bone Density and Geometry of the Upper Extremities after Stroke: A Case Report

The purpose of this study was to examine changes in bone density and geometry of the forearm region and motor function of the paretic upper extremity in a person with subacute stroke. Client Description: The participant was a 48-year-old man with right hemiparesis. Not applicable. Measures and Outcomes: The assessment of upper-extremity (UE) function and bone imaging took place at 3 months and 12 months after stroke. The participant had moderate motor impairment and severe disuse of the paretic UE 3 months after stroke. During the follow-up period, no substantial change in paretic UE function was observed. At the 12 month follow-up, the areal bone mineral density (aBMD) of the ultradistal and mid-regions of the paretic forearm, as measured by dual-energy X-ray absorptiometry, sustained a significant reduction of 7.9% and 5.9%, respectively. The non-paretic side, in contrast, had a significant 4.0% increase in aBMD of the mid-forearm and a 2.8% increase in aBMD of the total forearm. Significant findings from peripheral quantitative computed tomography were a reduction in total volumetric bone mineral density (-12.1%) and bone strength index (-20.6%) in the radius distal epiphysis on the paretic side and an increase in cortical bone mineral content (2.0%) and bone strength index (7.6%) in the radius diaphysis on the non-paretic side. After a stroke that resulted in moderate to severe UE impairment, a significant decline in bone mineral density was identified in various skeletal sites in the forearm region as the participant entered the subacute and chronic stages of recovery. The results point to the potential importance of early rehabilitative intervention in preventing unfavourable bone changes in the paretic upper limb among individuals with stroke.

Inhibition of Bone Loss byCissus quadrangularisin Mice: A Preliminary Report

Women drastically loose bone during and after menopause leading to osteoporosis, a disease characterized by low bone mass increasing the risk of fractures with minor trauma. Existing therapies mainly reduce bone resorption, however, all existing drugs have severe side effects. Recently, the focus is to identify alternative medicines that can prevent and treat osteoporosis with minimal or no side effects. We used Cissus quadrangularis (CQ), a medicinal herb, to determine its effects on bone loss after ovariectomy in C57BL/6 mice. Two-month old mice were either sham operated or ovariectomized and fed CQ diet. After eleven weeks, mice were sacrificed and the long bones scanned using pQCT and μCT. In the distal femoral metaphysis, femoral diaphysis, and proximal tibia, control mice had decreased cancellous and cortical bone, while CQ-fed mice showed no significant differences in the trabecular number, thickness, and connectivity density, between Sham and OVX mice, except for cortical bone mineral content in the proximal tibia. There were no changes in the bone at the tibio-fibular junction between groups. We conclude that CQ effectively inhibited bone loss in the cancellous and cortical bones of femur and proximal tibia in these mice.

Simulated resistance training, but not alendronate, increases cortical bone formation and suppresses sclerostin during disuse

Mechanical loading modulates the osteocyte-derived protein sclerostin, a potent inhibitor of bone formation. We hypothesized that simulated resistance training (SRT), combined with alendronate (ALEN) treatment, during hindlimb unloading (HU) would most effectively mitigate disuse-induced decrements in cortical bone geometry and formation rate (BFR). Sixty male, Sprague-Dawley rats (6-mo-old) were randomly assigned to either cage control (CC), HU, HU plus either ALEN (HU+ALEN), or SRT (HU+SRT), or combined ALEN and SRT (HU+SRT/ALEN) for 28 days. Computed tomography scans on days -1 and 28 were taken at the middiaphyseal tibia. HU+SRT and HU+SRT/ALEN rats were subjected to muscle contractions once every 3 days during HU (4 sets of 5 repetitions; 1,000 ms isometric + 1,000 ms eccentric). The HU+ALEN and HU+SRT/ALEN rats received 10 μg/kg ALEN 3 times/wk. Compared with the CC animals, HU suppressed the normal slow growth-induced increases of cortical bone mineral content, cortical bone area, and polar cross-sectional moment of inertia; however, SRT during HU restored cortical bone growth. HU suppressed middiaphyseal tibia periosteal BFR by 56% vs. CC (P < 0.05). However, SRT during HU restored BFR at both periosteal (to 2.6-fold higher than CC) and endocortical (14-fold higher than CC) surfaces (P < 0.01). ALEN attenuated the SRT-induced BFR gains during HU. The proportion of sclerostin-positive osteocytes in cortical bone was significantly higher (+121% vs. CC) in the HU group; SRT during HU effectively suppressed the higher proportion of sclerostin-positive osteocytes. In conclusion, a minimum number of high-intensity muscle contractions, performed during disuse, restores cortical BFR and suppress unloading-induced increases in sclerostin-positive osteocytes.

25-Hydroxyvitamin-D3 levels are positively related to subsequent cortical bone development in childhood: findings from a large prospective cohort study

SummaryIn exploring relationships between vitamin D status in childhood and cortical bone, little relationship was observed with plasma concentrations of 25-hydroxyvitamin-D2 [25(OH)D2], whereas 25-hydroxyvitamin-D3 [25(OH)D3] was positively related to cortical bone mineral content (BMCC) and cortical thickness, suggesting D3 exerts a beneficial effect on cortical bone development in contrast to D2.IntroductionThe study is aimed to determine whether vitamin D status in childhood is related to cortical bone development by examining prospective relationships between plasma concentrations of 25(OH)D2 and 25(OH)D3 at 7.6, 9.9 or 11.8 years and peripheral quantitative computed tomography (pQCT) measurements of the mid-tibia at age 15.5 years, in children from the Avon Longitudinal Study of Parents and Children.MethodsRelationships between vitamin D status and pQCT outcomes were analysed by bootstrap linear regression, adjusted for age, sex, body composition, socioeconomic position and physical activity, in 2,247 subjects in whom all covariates were available. 25(OH)D3 was also adjusted for season and 25(OH)D2, and 25(OH)D2 for 25(OH)D3.Results25(OH)D3 was positively related to BMCC [0.066(0.009,0.122), P = 0.02], whereas no association was seen with 25(OH)D2 [−0.008(−0.044,0.027), P = 0.7] [beta (with 95% CI) represents SD changes per doubling of vitamin D], P = 0.03 for difference in associations of 25(OH)D2 and 25(OH)D3 with BMCC. There were also differences in associations with cortical geometry, since 25(OH)D3 was positively related to cortical thickness [0.11(0.04, 0.19), P = 0.002], whereas no association was seen with 25(OH)D2 [−0.04(−0.08,0.009), P = 0.1], P = 0.0005 for difference. These relationships translated into differences in biomechanical strength as reflected by buckling ratio, which was positively related to 25(OH)D2 [0.06(0.01,0.11), P = 0.02] indicating less resistance to buckling, but inversely related to 25(OH)D3 [−0.1(−0.19,-0.02), P = 0.03], P = 0.001 for difference.ConclusionsIn contrast to 25(OH)D2, 25(OH)D3 was positively related to subsequent cortical bone mass and predicted strength. In vitamin D-deficient children in whom supplementation is being considered, our results suggest that D3 should be used in preference to D2.Electronic supplementary materialThe online version of this article (doi:10.1007/s00198-011-1813-9) contains supplementary material, which is available to authorized users.

Effects of age, vitamin D3, and fructooligosaccharides on bone growth and skeletal integrity of broiler chicks

A study was conducted to evaluate the effects of age, vitamin D(3), and fructooligosaccharides (FOS) on bone mineral density (BMD), bone mineral content (BMC), cortical thickness, cortical and trabecular area, and mechanical properties in broiler chicks using peripheral quantitative computed tomography and mechanical testing. A total of 54 male broiler chicks (1 d old) were placed in battery brooders and fed a corn-soybean starter diet for 7 d. After 7 d, the chicks were randomly assigned to pens of 3 birds each. Each treatment was replicated 3 times. There were 6 treatments: 1) early age control (control 1); 2) control 2; 3) 125 µg/kg of vitamin D(3); 4) 250 µg/kg of vitamin D(3); 5) 2% FOS); and 6) 4% FOS. The control 1 chicks were fed a control broiler diet and killed on d 14 to collect femurs for bone analyses. The remaining groups were killed on d 21. Femurs from 3-wk-old chicks showed greater midshaft cortical BMD, BMC, bone area, thickness, and marrow area than those from 2-wk-old chicks (P = 0.016, 0.0003, 0.0002, 0.01, and 0.0001, respectively). Total, cortical, and trabecular BMD of chick proximal femurs were not influenced by age. However, BMC and bone area were significantly affected by age. The femurs of 2-wk-old chicks exhibited significantly lower stiffness and ultimate load than those of 3-wk-old chicks (P = 0.0001), whereas ultimate stress and elastic modulus of the femurs of 2-wk-old chicks were significantly higher than that of femurs of 3-wk-old chicks (P = 0.0001). Chicks fed 250 µg/kg of vitamin D(3) exhibited significantly greater midshaft cortical BMC (P = 0.04), bone area (P = 0.04), and thickness (P = 0.03) than control 2, 2% FOS, or 4% FOS chicks. In summary, our study suggests that high levels of vitamin D(3) can increase bone growth and mineral deposition in broiler chicks. However, FOS did not have any beneficial effects on bone growth and skeletal integrity. Age is an important factor influencing skeletal integrity and mechanical properties in broiler chicks.

Yellow-bellied Marmots (Marmota flaviventris) preserve bone strength and microstructure during hibernation

Reduced skeletal loading typically results in decreased bone strength and increased fracture risk for humans and many other animals. Previous studies have shown bears are able to prevent bone loss during the disuse that occurs during hibernation. Studies with smaller hibernators, which arouse intermittently during hibernation, show that they may lose bone at the microstructural level. These small hibernators, like bats and squirrels, do not utilize intracortical remodeling. However, slightly larger mammals like marmots do. In this study we examined the effects of hibernation on bone structural, mineral, and mechanical properties in yellow-bellied marmots (Marmota flaviventris). This was done by comparing cortical bone properties in femurs and trabecular bone properties in tibias from marmots killed before hibernation (fall) and after hibernation (spring). Age data were not available for this study; however, based on femur length the post-hibernation marmots were larger than the pre-hibernation marmots. Thus, cross-sectional properties were normalized by allometric functions of bone length for comparisons between pre- and post-hibernation. Cortical thickness and normalized cortical area were higher in post-hibernation samples; no other normalized cross-sectional properties were different. No cortical bone microstructural loss was evident in osteocyte lacunar measurements, intracortical porosity, or intracortical remodeling cavity density. Osteocyte lacunar area, porosity, and density were surprisingly lower in post-hibernation samples. Trabecular bone volume fraction was not different between pre- and post-hibernation. Measures of both trabecular and cortical bone mineral content were higher in post-hibernation samples. Three-point bending failure load, failure energy, elastic energy, ultimate stress, and yield stress were all higher in post-hibernation samples. These results support the idea that, like bears, marmots are able to prevent disuse osteoporosis during hibernation, thus preventing increased fracture risk and promoting survival of the extreme environmental conditions that occur in hibernation.

Correlates of Osteoprotegerin and Association with Aortic Pulse Wave Velocity in Patients with Chronic Kidney Disease

Osteoprotegerin (OPG), a cytokine that regulates bone resorption, has been implicated in the process of vascular calcification and stiffness. Serum OPG was measured in 351 participants with chronic kidney disease (CKD) from one site of the Chronic Renal Insufficiency Cohort Study. Cortical bone mineral content (BMC) was measured by quantitative computed tomography in the tibia. Multivariable linear regression was used to test the association between serum OPG and traditional cardiovascular risk factors, measures of abnormal bone and mineral metabolism, and pulse wave velocity. Higher serum OPG levels were associated with older age, female gender, greater systolic BP, lower estimated GFR, and lower serum albumin. OPG was not associated with measures of abnormal bone or mineral metabolism including serum phosphorus, albumin-corrected serum calcium, intact parathyroid hormone, bone-specific alkaline phosphatase, or cortical BMC. Among 226 participants with concurrent aortic pulse wave velocity measurements, increasing tertiles of serum OPG were associated with higher aortic pulse wave velocity after adjustment for demographics, traditional vascular risk factors, and nontraditional risk factors such as estimated GFR, albuminuria, serum phosphate, corrected serum calcium, presence of secondary hyperparathyroidism, serum albumin, and C-reactive protein or after additional adjustment for cortical BMC in a subset (n = 161). These data support a strong relationship between serum OPG and arterial stiffness independent of many potential confounders including traditional cardiovascular risk factors, abnormal bone and mineral metabolism, and inflammation.

Osteoprotective Effect of Monascus-fermented Dioscorea in Ovariectomized Rat Model of Postmenopausal Osteoporosis

This experiment established the ovariectomized (OVX) rat model of postmenopausal osteoporosis and examined the effect of the oral administration of different dosages of dioscorea, red mold dioscorea (RMD), and soy isoflavones on bone mineral density (BMD). Three months after osteoporosis had been induced and 4 weeks after feeding had begun, the tibia and femur BMD of OVX rats administered RMD showed significant increases compared with that of all other groups of OVX rats. Closer examination using microcomputed tomography also revealed that the RMD-administered rats had denser trabecular bone volume and a higher trabecular number compared to all other rat groups. Reconstructed 3D imaging indicated increases in cancellous bone mineral content, cancellous bone mineral density, and cortical bone mineral content of the proximal tibia in OVX rats. These findings indicate that administration of monacolin K and phytoestrogen diosgenin could prevent bone loss induced by estrogen deficiency.

Reduced Bone Mass and Muscle Strength in Male 5α-Reductase Type 1 Inactivated Mice

Androgens are important regulators of bone mass but the relative importance of testosterone (T) versus dihydrotestosterone (DHT) for the activation of the androgen receptor (AR) in bone is unknown. 5α-reductase is responsible for the irreversible conversion of T to the more potent AR activator DHT. There are two well established isoenzymes of 5α-reductase (type 1 and type 2), encoded by separate genes (Srd5a1 and Srd5a2). 5α-reductase type 2 is predominantly expressed in male reproductive tissues whereas 5α-reductase type 1 is highly expressed in liver and moderately expressed in several other tissues including bone. The aim of the present study was to investigate the role of 5α-reductase type 1 for bone mass using Srd5a1−/− mice. Four-month-old male Srd5a1 −/− mice had reduced trabecular bone mineral density (−36%, p<0.05) and cortical bone mineral content (−15%, p<0.05) but unchanged serum androgen levels compared with wild type (WT) mice. The cortical bone dimensions were reduced in the male Srd5a1 −/− mice as a result of a reduced cortical periosteal circumference compared with WT mice. T treatment increased the cortical periosteal circumference (p<0.05) in orchidectomized WT mice but not in orchidectomized Srd5a1 −/− mice. Male Srd5a1 −/− mice demonstrated a reduced forelimb muscle grip strength compared with WT mice (p<0.05). Female Srd5a1 −/− mice had slightly increased cortical bone mass associated with elevated circulating levels of androgens. In conclusion, 5α-reductase type 1 inactivated male mice have reduced bone mass and forelimb muscle grip strength and we propose that these effects are due to lack of 5α-reductase type 1 expression in bone and muscle. In contrast, the increased cortical bone mass in female Srd5a1 −/− mice, is an indirect effect mediated by elevated circulating androgen levels.

Thirteen-lined ground squirrels (Ictidomys tridecemlineatus) show microstructural bone loss during hibernation but preserve bone macrostructural geometry and strength

Lack of activity causes bone loss In most animals. Hibernating bears have physiological processes to prevent cortical and trabecular bone loss associated with reduced physical activity, but different mechanisms of torpor among hibernating species may lead to differences in skeletal responses to hibernation. There are conflicting reports regarding whether small mammals experience bone loss during hibernation. To investigate this phenomenon, we measured cortical and trabecular bone properties in physically active and hibernating juvenile and adult 13-lined ground squirrels (Ictidomys tridecemlineatus, previous genus name Spermophilus). Cortical bone geometry, strength and mineral content were similar in hibernating compared with active squirrels, suggesting that hibernation did not cause macrostructural cortical bone loss. Osteocyte lacunar size increased (linear regression, P=0.001) over the course of hibernation in juvenile squirrels, which may indicate an osteocytic role in mineral homeostasis during hibernation. Osteocyte lacunar density and porosity were greater (+44 and +59%, respectively; P<0.0001) in hibernating compared with active squirrels, which may reflect a decrease in osteoblastic activity (per cell) during hibernation. Trabecular bone volume fraction in the proximal tibia was decreased (-20%; P=0.028) in hibernating compared with physically active adult squirrels, but was not different between hibernating and active juvenile squirrels. Taken together, these data suggest that 13-lined ground squirrels may be unable to prevent microstructural losses of cortical and trabecular bone during hibernation, but importantly may possess a biological mechanism to preserve cortical bone macrostructure and strength during hibernation, thus preventing an increased risk of bone fracture during remobilization in the spring.

Changes in cortical bone mineralization in the mouse mandible with regenerated condyle

The objective of this study was to evaluate the effects of condylectomy and of a functional appliance on the mineral content, density, and area of the mandibular cortical bone in a growing mouse model. In the condylectomy group, a unilateral condylectomy was performed on the right side of the mouse mandible. In the condylectomy + appliance group, a functional appliance was used to reposition the mandible after the unilateral condylectomy. All mice were killed 4 wk after surgery. Each mandible was then subjected to analyses of cortical bone mineral content (CRT_CNT), cortical bone density (CRT_DEN), and cortical bone area (CRT_A) by peripheral quantitative computed tomography (pQCT). The CRT_CNT, CRT_DEN, and CRT_A values were significantly lower in the condylectomized mandible (right side) than in the non-condylectomized mandible (left side). However, in the condylectomized animals in which a functional appliance was used, the CRT_CNT, CRT_DEN, and CRT_A values became higher than those in the mice treated with condylectomy alone. No significant differences were found in the CRT_CNT, CRT_DEN, and CRT_A between non-condylectomized (left side) mandibles, mandibles treated with condylectomy + functional appliance (right side), and control mandibles. It was thus shown that a functional appliance used to reposition the condylectomized mandible forward in a symmetric position induced improvement of the cortical bone in a mouse model in terms of cortical bone mineral content, density, and area.