Total Bone Content Research Articles

Involvement of the vitamin D receptor gene in the development of idiopathic short stature

Background. The vitamin D receptor (VDR) gene is localized in the chromosome 12 (region 12q13). Its polymorphic variants BsmI and FokI are the most promising in clinical and diagnostic terms. During normal ontogenesis, the VDR gene affects the total bone content in the body and its resulting length determined by the development of the skeleton. The aim of the study was to assess genotypic features in children with idiopathic short stature. Materials and methods. Determination of the BsmI polymorphism in the VDR gene (rs1544410) was performed by polymerase chain reaction followed by analysis of the length of restriction fragments when detected by agarose gel electrophoresis in 18 prepubertal children with idiopathic short stature. Results. In the group of children with idiopathic short stature, the proportion of the GG genotype is four times higher than in the control group. In children of the G/A heterozygotes, the risk of idiopathic short stature is significantly high (odds ratio (OR)=6.00; 95% confidence interval (CI) 2.06–17.48; p<0.01); in the G/G variant, it is high but not significant (OR=4.54; 95% CI 0.70–29.31; p=0.11). Patients with the AA genotype were three times less than in the control group, indicating that the AA homozygotes have a threefold reduction in the risk of idiopathic short stature compared to an empirical risk. The frequency of the G allele in patients (qG=0.444) is almost three times higher than in the group of healthy individuals (qG=0.152), indicating that the carriage of the G allele of the rs1544410 BsmI polymorphic locus of the VDR gene is significantly associated with the risk of developing idiopathic short stature (OR=4.46; 95% CI 3.60–5.51; p<0.001). Conclusions. In children with the G/A and G/G genotypes, the risk of idiopathic short stature increases, and the presence of the A/A genotype is a protective polymorphism against idiopathic short stature. Carriage of the G allele of the rs1544410 BsmI polymorphic locus of the VDR gene is associated with the risk of idiopathic short stature, despite the almost perfect distribution of genotypes.

The Mid-Diaphysis Is a Poor Predictor of Humeral Fracture Risk Indicating That Predisposing Factors Are Recent

The incidence of spontaneous humeral fractures in first-lactation dairy heifers in New Zealand has emphasised the need to understand the thoracic limb bone growth of dairy heifers. Previous research has indicated that a predisposing factor to spontaneous humeral fracture is nutrition. In addition, it has been hypothesised that liver copper concentration affects bone strength and may be a potential factor associated with humeral fracture risk. The aim of this study was to compare bone morphology in the mid-diaphysis of the metacarpus and humerus of heifers affected and unaffected by spontaneous humeral fractures, and determine the effect of copper status at death on bone morphology. The metacarpus and humerus were collected from heifers affected and unaffected by humeral fractures, and scanned using peripheral quantitative computed tomography (pQCT). The mid-diaphysis of the humerus of the affected group had reduced cortical bone mineral density and a trend for reduced cortical content and total bone content, which contributed to a reduced stress–strain index. The trend for reduced bone length in affected humeri provides additional support for the hypothesis of inhibited humeral growth. Heifers with low copper liver concentrations had reduced humerus lengths and reduced cortical bone mineral densities. These data support the hypothesis that the developmental window for humeral fracture is recent, and possibly associated with periods of inadequate nutrition.

Bone Health of Young Male Gymnasts: A Systematic Review.

To synthesize existing literatures on the impact of gymnastics participation on the skeletal health of young male gymnasts. Following a systematic search, 12 studies were included in this review. Quality of included studies was assessed using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE modified) criteria. Assessment of skeletal health varied between and within imaging modality protocols. Gymnasts had higher total bone content, greater total and trabecular bone density, larger bone size, a thicker cortex, and higher estimates of bone strength than controls. Recreational studies reported no difference in height or weight between gymnasts and controls; however, elite gymnasts were shorter and lighter than nongymnasts. STROBE scores ranged from 65% to 95%. Gymnastics participation may be beneficial to the bone health of young males as gymnasts had higher bone density and bone mineral content, larger bones, and greater estimates of bone strength than controls.

Skeletal Characteristics of Competitive Female Rowers

Weight-supported activities, such as rowing, are not commonly prescribed for fracture prevention. However, rowing requires large magnitudes of internal loading, thus it has potential to induce positive skeletal adaptations, especially in the hip and radius, two common fracture sites. PURPOSE: To examine skeletal health and body composition in college aged competitive female rowers. METHODS: In this cross-sectional study, 24 rowers and 24 age and body mass (±2yrs and 5lbs) matched physically active controls were compared. DXA was used to measure body composition and areal BMD (aBMD) of the total body, lumbar spine, hips and forearms, and hip structural analysis variables. pQCT was used to assess bone characteristics and bone strength of the tibiae (4%, 38%, 66%) and radii (4%, 66%) sites. RESULTS: Age- and height-adjusted aBMDs were not significantly different between groups (p>0.05), but rowers had greater hip cross-sectional moment of inertia (p≤0.05). Rowers had greater tibiae 4% total area, trabecular area, and periosteal circumference (PeriC) (p≤0.05). Also, total bone content and area, cortical area, PeriC, iPolar and SSI were greater at the tibiae 38% and 66% sites for rowers (p≤0.05). Controls had significantly greater 38% tibiae cortical density than rowers (p≤0.05). Rowers had significantly greater forearm muscle cross sectional area (p≤0.01) at the 66% radial site, and greater PeriC at the 4% radial site (p≤0.05). CONCLUSIONS: Rowers had greater tibiae bone area and strength compared to controls, but there were no group differences in aBMD or most radial bone variables. Our findings suggest that competitive rowing has osteogenic potential and may be particularly beneficial for improving bone quality at the tibiae even when compared to physically active controls.Table 1: Group comparisons of mean bilateral skeletal characteristics (means±SE)

Effects of Ibuprofen and Resistance Training on Bone and Muscle: A Randomized Controlled Trial in Older Women.

Resistance training with ibuprofen supplementation may improve musculoskeletal health in postmenopausal women. The study purpose was to determine the efficacy of resistance training and ibuprofen supplementation on bone and muscle properties in postmenopausal women. Participants (n = 90, 65.3 ± 4.9 yr) were randomly assigned to: supervised resistance training or stretching (placebo-exercise) with postexercise ibuprofen (400 mg) or placebo supplementation for 3 d·wk (9 months). Baseline and postintervention measurements included distal and shaft scans of the forearm and lower leg using peripheral quantitative computed tomography. Distal site outcomes included cross-sectional area, content, and density for total and trabecular bone, as well as estimated bone strength in compression. Shaft site outcomes included total bone area; cortical bone area, content, and density; estimated bone strength in torsion; and muscle area and density. Exercise-supplement-time interactions for total bone content at the distal radius (P = 0.009) and cortical density at the radius shaft (P = 0.038) were significant. Resistance training with ibuprofen decreased total bone content (-1.5%) at the distal radius in comparison to the resistance training (0.6%; P = 0.032) and ibuprofen alone (0.5%; P = 0.050). Change in cortical density at the radius shaft differed between the stretching with placebo and ibuprofen supplementation groups (-1.8% vs 1.1%; P = 0.050). Resistance training preserved muscle density in the lower leg more so than stretching (-3.1% vs -5.4%; P = 0.015). Ibuprofen consumed immediately after resistance training had a deleterious effect on bone mineral content at the distal radius, whereas resistance training or ibuprofen supplementation individually prevented bone loss. Resistance training prevented muscle density decline in the lower leg.

A longitudinal study of bone area, content, density, and strength development at the radius and tibia in children 4-12 years of age exposed to recreational gymnastics.

This study investigated the long-term relationship between the exposure to childhood recreational gymnastics and bone measures and bone strength parameters at the radius and tibia. It was observed that individuals exposed to recreational gymnastics had significantly greater total bone content and area at the distal radius. No differences were observed at the tibia. This study investigated the relationship between exposure to early childhood recreational gymnastics with bone measures and bone strength development at the radius and tibia. One hundred twenty seven children (59 male, 68 female) involved in either recreational gymnastics (gymnasts) or other recreational sports (non-gymnasts) between 4 and 6 years of age were recruited. Peripheral quantitative computed tomography (pQCT) scans of their distal and shaft sites of the forearm and leg were obtained over 3 years, covering the ages of 4-12 years at study completion. Multilevel random effects models were constructed to assess differences in the development of bone measures and bone strength measures between those exposed and not exposed to gymnastics while controlling for age, limb length, weight, physical activity, muscle area, sex, and hours of training. Once age, limb length, weight, muscle area, physical activity, sex, and hours of training effects were controlled, it was observed that individuals exposed to recreational gymnastics had significantly greater total bone area (18.0 ± 7.5 mm(2)) and total bone content (6.0 ± 3.0 mg/mm) at the distal radius (p < 0.05). This represents an 8-21 % benefit in ToA and 8-15 % benefit to ToC from 4 to 12 years of age. Exposure to recreational gymnastics had no significant effect on bone measures at the radius shaft or at the tibia (p > 0.05). Exposure to early life recreational gymnastics provides skeletal benefits to distal radius bone content and area. Thus, childhood recreational gymnastics exposure may be advantageous to bone development at the wrist.

Clinical profile of patients with renal calculi attending a bone health clinic

Clinical profile of patients with renal calculi attending a bone health clinic

Precompetitive and recreational gymnasts have greater bone density, mass, and estimated strength at the distal radius in young childhood

Young recreational and precompetitive gymnasts had, on average, 23% greater bone strength at the wrist compared to children participating in other recreational sports. Recreational gymnastics involves learning basic movement patterns and general skill development and as such can easily be implemented into school physical education programs potentially impacting skeletal health. Competitive gymnasts have greater bone mass, density, and estimated strength. The purpose of this study was to investigate whether the differences reported in the skeleton of competitive gymnasts are also apparent in young recreational and precompetitive gymnasts. One hundred twenty children (29 gymnasts, 46 ex-gymnasts, and 45 non-gymnasts) between 4 and 9years of age (mean = 6.8 ± 1.3) were measured. Bone mass, density, structure, and estimated strength were determined using peripheral quantitative computed tomography at the distal (4%) and shaft (65%, 66%) sites in the radius and tibia. Total body, hip, and spine bone mineral content (BMC) was assessed using dual energy X-ray absorptiometry. Analysis of covariance (covariates of sex, age and height) was used to investigate differences in total bone content (ToC), total bone density (ToD), total bone area (ToA), and estimated strength (BSI) at the distal sites and ToA, cortical content (CoC), cortical density (CoD), cortical area (CoA), cortical thickness, medullary area, and estimated strength (SSIp) at the shaft sites. Gymnasts and ex-gymnasts had 5% greater adjusted total body BMC and 6-25% greater adjusted ToC, ToD, and BSI at the distal radius compared to non-gymnasts (p < 0.05). Ex-gymnasts had 7-11% greater CoC and CoA at the radial shaft and 5-8% greater CoC and SSIp at the tibial shaft than gymnasts and non-gymnasts. Ex-gymnasts also had 12-22% greater ToC and BSI at the distal tibia compared to non-gymnasts (p < 0.05). This data suggests that recreational and precompetitive gymnastics participation is associated with greater bone strength.

Experimental results of combining bisphosphonates with allograft in a rat model

Soaking bone grafts in a bisphosphonate solution before implantation can prevent their resorption and increase the local bone density in rats and humans. However, recent studies suggest that pre-treatment of allografts with bisphosphonate can prevent bone ingrowth into impaction grafts. We tested the hypothesis that excessive amounts of bisphosphonate would also cause a negative response in less dense grafts. We used a model where non-impacted metaphyseal bone grafts were randomised into three groups with either no bisphosphonate, alendronate followed by rinsing, and alendronate without subsequent rinsing, and inserted into bone chambers in rats. The specimens were evaluated histologically at one week, and by histomorphometry and radiology at four weeks. At four weeks, both bisphosphonate groups showed an increase in the total bone content, increased newly formed bone, and higher radiodensity than the controls. In spite of being implanted in a chamber with a limited opportunity to diffuse, even an excessive amount of bisphosphonate improved the outcome. We suggest that the negative results seen by others could be due to the combination of densely compacted bone and a bisphosphonate. We suggest that bisphosphonates are likely to have a negative influence where resorption is a prerequisite to create space for new bone ingrowth.

Comparison and precision of the XCT 3000 and XCT 2000 peripheral quantitative computer tomography densitometers for geometric and material bone parameters of the radius

Use of peripheral quantitative computed tomography (pQCT) in research has increased in the past decade. This study compares bone measures from two pQCT densitometers: the XCT3000 and the XCT2000 (Orthometrix Inc., White Plains, NY). Coefficients of variation (CV) for the XCT3000 also are reported.Images from the distal radius (4% site) and radial shaft (20% site) in 35 (19 male) healthy individuals were obtained using the XCT2000 and XCT3000. Age ranged from 13–75 years (mean 32 years). Mean height was 172.7±11.3 cm and weight was 77.0±20.6 kg. CVs for the XCT3000 were calculated from duplicate scans and ranged from 1.3% for total bone content to 7.5% for trabecular bone content (4% site) and from 0.7% for cortical volumetric bone mineral density to 2.7% for endosteal circumference (20% site). There were no differences in the means of any of the bone measures between the two machines. Strong associations between the XCT2000 and XCT3000 measures were noted (R‐value ranging from 0.92 to 1.0). Trabecular density and total bone content (4% site) had mean differences (XCT3000‐XCT2000) not equal to zero, other bone measure mean differences were not different from zero. Adjustments between the machines may need to be made for trabecular density and total bone content at the 4% site.Supported by: EA Martin Program in Human Nutrition at South Dakota State University.

Osteopenia and impaired fracture healing in aged EP4 receptor knockout mice

The EP4 receptor, one of the subtypes of the prostaglandin E 2 (PGE 2) receptor, plays a critical role in the anabolic effects of PGE 2 on bone. However, its role in the maintenance of bone mass in aged animals and its role in fracture healing is not well known. Our studies addressed these issues by characterizing the skeletal phenotype of aged, EP4 receptor knockout (KO) mice, and by comparing fracture healing in aged KO mice versus wild type (WT) mice. There was no significant difference in body weight and femoral length between KO and WT mice at 15 to 16 months of age. Lower bone mass was seen radiographically in both axial and long bones of KO mice relative to WT mice. Micro-CT images of the distal femurs showed thinner cortices, fewer trabeculae, and a deteriorated trabecular network in KO mice. Total bone content, trabecular content, and cortical content, as assessed by pQCT in the distal femur, were lower in KO mice than WT controls. Histomorphometric measurements showed that trabecular bone volume and bone formation rate were significantly decreased whereas osteoclast number on trabecular surface and eroded surface on endocortical surface were significantly increased in KO mice. These data indicated that deleting the EP4 receptor resulted in an imbalance in bone resorption over formation, leading to a negative bone balance. The lower bone formation rate in EP4 KO mice was primarily due to decreased mineralizing surface, suggesting that the defect in overall bone formation was mainly due to the defect in osteoblastogenesis. Fracture healing was examined in KO and WT mice subjected to a transverse femoral fracture. Callus formation was significantly delayed as evidenced both radiographically and histologically in the fractured femurs of KO mice compared with those of WT mice. KO mice had significant decreases in total callus area, cartilaginous callus area, and bony callus area 2 weeks after fracture. By 4 weeks, complete bony bridging was seen in WT mice but not in KO mice. These data demonstrate that the absence of the EP4 receptor decreases bone mass and impairs fracture healing in aged male mice. Our findings indicate that the EP4 receptor is a positive regulator in the maintenance of bone mass and fracture healing.

Both Resistance and Agility Training Increase Cortical Bone Density in 75- to 85-Year-Old Women With Low Bone Mass

A randomized, controlled, single-blinded 25-wk prospective study was conducted to compare the effects of group-based resistance and agility training on bone, as measured by both dual-energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT), in older women with low bone mass. Ninety-eight community-dwelling women aged 75-85 yr were randomized to one of three experimental groups: resistance training (n = 32), agility training (n = 34), or stretching (sham exercise) (n = 32). Total hip, femoral neck, and trochanteric bone mineral density (BMD) were measured by DXA. Peripheral QCT measurements were performed at the tibia and radius. The pQCT outcome measures at the shaft regions were cortical bone content, cortical bone cross-sectional area, cortical bone density, and density-weighted polar section modulus (SSI). The pQCT outcome measures at the distal sites were total bone content, total bone cross-sectional area, and total bone density. At trial completion, the agility training group significantly increased cortical bone density by 0.5 +/- 0.2% (SE) at the tibial shaft compared with a 0.4 +/- 0.3% loss in the stretching group. The resistance training group significantly increased cortical bone density (1.4 +/- 0.6%) at the radial shaft compared, with a 0.4 +/- 0.5% loss in the agility training group. No significant between-group differences were observed in the other bone outcome measures (by DXA or pQCT). Future research is needed to determine the mechanism(s) responsible for the observed adaptation of the cortical bone to mechanical loading.

Factors affecting knee cartilage volume in healthy men.

To understand the factors that influence joint cartilage in health and disease as they are important for the prevention and management of osteoarthritis. We conducted a cross-sectional study to determine factors influencing knee cartilage volume in 45 males aged (mean+/-S.D.) 52.5+/-13.2 yr. Total and medial tibial volumes were inversely associated with age, body mass index (BMI) and amount of physical activity and positively associated with total bone content. BMI explained the largest amount of the variation in tibial cartilage volume (18.7%). There were similar findings at the lateral tibial cartilage, but for age and total bone content this did not reach statistical significance. There was a positive association with serum testosterone at all tibial cartilage sites, but this only reached statistical significance for medial tibial cartilage, where serum testosterone explained up to 8% of the variation in cartilage volume. Modifiable risk factors of osteoarthritis also appear to be significant determinants of tibial cartilage volume. Serum testosterone may provide one possible explanation for gender differences in tibial cartilage volume and prevalence of tibiofemoral osteoarthritis. The proposed link between osteoarthritis and knee cartilage volume and the effect of testosterone will need to be confirmed in longitudinal studies.

Treating Ununited Fractures with Electricity: Nursing Implications

Not only are the elderly more susceptible to fractures because of a decrease in total bone content from osteoporosis, but the regeneration of injured bone may be prolonged as well. When a long bone fracture occurs in the elderly person, weightlessness and immobility result in further acceleration of bone loss. Because the success of pulsing electromagnetic field treatments depends on adherence to the treatment protocol, patient education is a key in nursing care. Although all fractures are a serious setback for the elderly person, those that do not heal properly require special considerations and the mobilization of many resources if the patient is to remain out of an institution.