Wrist Bone Mineral Density Research Articles

Bone bending strength and BMD of female athletes in volleyball, soccer, and long-distance running.

The purpose of the study was to determine whether sports training comprised of (1) high-impact loading sport in volleyball (VOL), (2) odd impact loading sport in soccer (SOC), and (3) low impact sport in distance running (RUN) were associated with tibial bending strength and calcaneus bone mineral density (BMD), and ulnar bending strength and wrist BMD. Female athletes comprised of 13 VOL, 22 SOC, and 22 RUN participated in the study. Twenty-three female non-athletes (NA) served as the comparison group. Tibial and ulnar bending strength (EI, Nm2) were assessed using a mechanical response tissue analyzer (MRTA). Calcaneus and wrist BMD were assessed using a peripheral X-ray absorptiometry. Group means differences among the study groups were determined using ANCOVA with age, weight, height, percent body fat, ethnicity/race, and training history serving as covariates. Tibial EI of VOL (228.3 ± 138Nm2) and SOC (208.6 ± 115Nm2) were greater (p < 0.05) compared to NA (101.2 ± 42Nm2). Ulnar EI of SOC (54.9 ± 51Nm2) was higher (p < 0.05) than NA (27.2 ± 9Nm2). Calcaneus BMD of VOL (0.618 ± 0.12g/cm2), SOC (0.621 ± 0.009g/cm2), and RUN (0.572 ± 0.007g/cm2) were higher (p < 0.05) than NA (0.501 ± 0.08g/cm2), but not different between athletic groups. Wrist BMD of VOL (0.484 ± .06g/cm2) and SOC (0.480 ± 0.06g/cm2) were higher (p < 0.05) than NA (0.443 ± 0.04g/cm2). Female VOL athletes exhibit greater tibial bending strength than RUN and NA, but not greater than SOC. Female SOC athletes exhibit greater ulnar bending strength and wrist BMD than NA.

Relation between Hand Bone Mineral Density, Degree of Joint Destruction, and Hand Function in Adults Rheumatoid Arthritis Patients

Background: Rheumatoid Arthritis [RA] is a chronic systemic disease that affects the functional capacity of the hand due to inflammatory arthritis and joint destruction. RA patients have difficulties with everyday life activities and daily living activities. The prevalence of osteoporosis is estimated to be about twice that of the general population. Dual-energy X-ray absorptiometry (DEXA) is the most precise tool for detecting loss in bone mineral density in RA.&#x0D; Aim of the study: This study aims to investigate the relation between generalized bone mineral density (BMD) and each of hand joint destruction and hand function in order to find out its possible role in assessment of rheumatoid hand disability.&#x0D; Patients and Methods: Fifty patients diagnosed as RA based on the 2010 ACR Rheumatoid Arthritis Classification Criteria were included in this study. All patients were subjected to the following scores: Duruöz Hand Index (DHI), Grip Ability Test (GAT), Grip strength test, and Pinch strength tests for assessing the function of the dominant hand of each patient. The participants were also subjected to plain x-ray evaluated by van der Heijde-modified total Sharp score (vdH-S) to assess the damage of the joints of the dominant hand, and Dual-energy X-ray absorptiometry (DEXA) to assess the Bone Mineral Density.&#x0D; Results: The current study showed that wrist BMD was correlated with grip strength, pinch strength, GAT, and van der Heijde modified sharp score of the dominant hand. Moreover, X-ray joint findings were significantly correlated with each of total grip ability test, grip strength, and pinch strength as the hand disability manifested more with joint damage.&#x0D; Conclusion: In conclusion, Osteoporosis, hand function, and joint damage in RA are correlated suggesting related pathophysiological mechanisms. The Severity of RA could be related to osteoporosis as well as joint destruction and hand disability.

Whole-body morphological asymmetries in high-level female tennis players: A cross‑sectional study

ABSTRACT This cross-sectional study aimed to examine the degree of whole-body morphological asymmetries in female tennis players. Data were collected in 19 high-level female tennis players (21.3 ± 3.4 years). Based on anthropometric measurements (upper arm, lower arm, wrist, upper leg and lower leg circumferences as well as elbow and knee widths) and dual x-ray absorptiometry research scans (bone mineral density (BMD), bone mineral content (BMC), lean mass (LM), fat mass (FM) as well as humerus, radio-ulnar, femur and tibia bone lengths), within-subject morphological asymmetries for both upper (dominant vs. non-dominant) and lower (contralateral vs. ipsilateral) extremities were examined. Upper arm (p = 0.015), lower arm (p < 0.001) and wrist circumferences (p < 0.001), elbow width (p = 0.049), BMD (p < 0.001), BMC (p < 0.001), LM (p = 0.001), humerus (p = 0.003) and radio-ulnar bone length (p < 0.001) were all greater in the dominant upper extremity. BMC (p < 0.001) and LM (p < 0.001) were greater in the contralateral lower extremity, whereas FM (p = 0.028) was greater in the ipsilateral lower extremity. This is the first study to report significant side-to-side differences in both upper and lower extremities in high-level female tennis players.

Assessment of Agreement of Wrist Bone Mineral Density with Spine and Hip Bone Mineral Density in Postmenopausal Women

Objective: Worldwide, osteoporosis in postmenopausal women is a common public health problem. The measurement of bone mineral density (BMD) of spine and hip using central dual energy X-ray absorptiometry (DXA) is the most standard technique to diagnose osteoporosis. But in many circumstances, measurement of spine or hip BMD is quite difficult to carry out where wrist BMD can be used as an alternative. Moreover, wrist BMD can be done with smaller, cheaper, portable peripheral devices for screening osteoporosis at primary health care level. The objective of the study was to explore the agreement of wrist BMD with spine and hip BMD in postmenopausal women.&#x0D; Patients and Methods: This observational, cross sectional study was carried out at National Institute of Nuclear Medicine &amp; Allied Sciences (NINMAS), Bangabandhu Sheikh Mujib Medical University (BSMMU) campus, from July 2017 to June 2018. A total of 110 postmenopausal women referred to NINMAS for BMD measurement were enrolled in this study after fulfilling selection criteria. BMD of spine, right and left hip and wrist of enrolled subjects were measured by dual energy X-ray absorptiometry (DXA) scan by Stratos DR Bone densitometer.&#x0D; Results: Agreement analysis done by kappa statistics revealed kappa value of 0.930 (p&lt;0.05), 0.782 (p&lt;0.05) and 0.635 (p&lt;0.05) between wrist and spine BMD, wrist and right hip BMD and wrist and left hip BMD, respectively. In Bland-Altman analysis, the mean difference of T-score measured by wrist and spine was -0.007 ± 1.361, wrist and right hip was -0.645 ± 1.271 and wrist and left hip was -0.450 ± 1.259 with 95% of differences were found in between -2.674 and 2.660, -3.136 and 1.846 and -2.917 and 2.017, respectively. Positive significant Pearson’s correlation was observed between wrist BMD and spine BMD (r=0.664; p=0.001), wrist BMD and right hip BMD (r=0.719; p=0.001) and wrist BMD and left hip BMD (r=0.727; p=0.001).&#x0D; Conclusion: This study results showed an excellent kappa agreement between wrist and spine BMD with good kappa agreement of wrist with right and left hip BMD as well as in Bland-Altman analysis, the mean differences of T-score between wrist andspine, wrist and right hip and wrist and left hip were small. The biases between the methods were considered not significant suggesting that these sites can be used interchangeably for measurement of BMD. Hence, wrist BMD can be used with regular skeletal sites (spine and hip) as an effective method of diagnosing osteopenia and osteoporosis by DXA where spine or hip BMD is difficult to carry out as well as it can be used for osteoporosis screening at primary health care level by portable peripheral DXA device to initiate early treatment to reduce fracture risks.&#x0D; Bangladesh J. Nuclear Med. 22(1): 41-46, Jan 2019

Denosumab effects on serum levels of the bone morphogenetic proteins antagonist noggin in patients with transfusion-dependent thalassemia and osteoporosis

ABSTRACTIntroduction: Noggin is an antagonist of bone morphogenetic proteins (BMPs) and has a strong effect on osteogenesis. Osteoporosis is a common complication of transfusion dependent beta-thalassemia (TDT) and denosumab has been recently emerged as a promising therapeutic option. This was a post hoc investigation of serum noggin levels among TDT patients with osteoporosis who participated in a randomized, placebo-control, phase 2b study.Methods: Patients received either 60 mg denosumab (n = 32) or placebo (n = 31) every 6 months for 12 months. Noggin was measured, for the first time in thalassemia patients, at baseline and at 12 months, using a recently developed high sensitivity fluorescent immunoassay.Results: Both groups showed a significant increase in noggin serum levels (denosumab p < 0.001; placebo p < 0.0001). Interestingly, the increase was higher in the placebo group. Furthermore, we observed a strong correlation between noggin and wrist bone mineral density (r = −0.641, p = 0.002) only in the denosumab group.Conclusion: In conclusion, higher noggin levels reflected more BMP inhibition, since our assay detects free bioactive noggin, which in turn impaired bone formation in placebo group. Therefore, denosumab possibly regulates noggin and favours bone turnover in TDT patients with osteoporosis through a novel mechanism of action.Trial registration: ClinicalTrials.gov identifier: NCT02559648.

Denosumab in transfusion-dependent thalassemia osteoporosis: a randomized, placebo-controlled, double-blind phase 2b clinical trial

AbstractDenosumab (DNM) is a fully human monoclonal antibody against the receptor activator of nuclear factor kappa-B ligand (RANKL) that has been licensed for the treatment of different types of osteoporosis. However, the prospective data for the evaluation of DNM efficacy on transfusion-dependent thalassemia (TDT)–induced osteoporosis are rather limited. Thus, we conducted a randomized, placebo-controlled, double-blind, phase 2b clinical trial to evaluate DNM in TDT osteoporosis. Patients were assigned to receive either 60 mg DNM (n = 32) or placebo (n = 31) subcutaneously on day 0 and 180 during a total of 12 months of follow-up. The percentage increase of L1-L4 bone mineral density was higher in the DNM group than the placebo group (5.92% ± 5.25% vs 2.92% ± 5.56%, respectively; P = .043), whereas the advantage of DNM regarding wrist bone mineral density was much higher compared with placebo (−0.26% ± 5.31% vs −3.92% ± 8.71%, respectively; P = .035). No grade 3 or 4 toxicity was observed. DNM reduced pain scores that remained unaltered in the placebo group. DNM showed a significant reduction of soluble RANKL (sRANKL), sRANKL/osteoprotegerin ratio, C-telopeptide of collagen type I, tartrate-resistant acid phosphatase isoform-5b, and bone-specific alkaline phosphatase between baseline and the 12th month (P < .01 for all comparisons) without changes in dickkopf-1, sclerostin, and osteocalcin. On the contrary, placebo patients showed an increase in sRANKL, osteoprotegerin, dickkopf-1, sclerostin, C-telopeptide of collagen type I, tartrate-resistant acid phosphatase isoform-5b, and bone-specific alkaline phosphatase during the study period (P < .01 for all comparisons). In conclusion, DNM increased lumbar spine and wrist bone mineral density and reduced pain and bone remodeling markers, and thus it is another valuable option for the management of TDT-induced osteoporosis. This trial was registered at www.clinicaltrials.gov as #NCT02559648.

The burden and undertreatment of fragility fractures among senior women.

The purpose of the study is to estimate prevalence of fragility fractures (FF), risk factors, and treatment rates in senior women and to assess impact of FF on physical function and quality of life. Women aged 65years and older from the EpiReumaPt study (2011-2013) were evaluated. Rheumatologists collected data regarding FF, clinical risk factors for fractures, and osteoporosis (OP) treatment. Health-related quality of life (EQ5D) and physical function (HAQ) were analyzed. Peripheral dual-energy X-ray absorptiometry was performed. FF was defined as any self-reported low-impact fracture that occurred after 40years of age. Prevalence estimates of FF were calculated. Among 3877 subjects evaluated in EpiReumaPt, 884 were senior women. The estimated prevalence of FF was 20.7%. Lower leg was the most frequent fracture site reported (37.8%) followed by wrist (18.6%). Only 7.1% of the senior women reporting a prevalent FF were under treatment for OP, and 13.9% never had treatment. OP treatment was not prescribed in 47.7% of FF women, and 23.4% refused treatment. Age (OR = 2.46, 95% CI 1.11-5.47), obesity (OR = 2.05, 95% CI 1.14-3.70), and low wrist BMD (OR = 2.29; 95% CI 1.20, 4.35; p = 0.012) were positively associated with prevalent FF. A significantly higher proportion of women in the lowest quintile of wrist bone mineral density reported FF (OR = 2.29, 95% CI 1.20-4.35). FF were associated with greater physical disability (β = 0.33, 95% CI 0.13-0.51) independent of other comorbidities. FF was frequently reported among senior women as an important cause of physical disability. However, the prevalence of OP treatment was low, which constitutes a public health problem in this vulnerable group.

Osteoprotegerin autoantibodies do not predict low bone mineral density in middle-aged women

PurposeAutoantibodies against osteoprotegerin (OPG) have been associated with osteoporosis. The aim was to develop an immunoassay for OPG autoantibodies and test their diagnostic usefulness of identifying women general population with low bone mineral density. MethodsIncluded were 698 women at mean age 55.1years (range 50.4–60.6) randomly selected from the general population. Measurement of wrist bone mineral density (g/cm2) was performed of the non-dominant wrist by dual-energy X-ray absorptiometry (DXA). A T-score<−2.5 was defined as having a low bone mineral density. Measurements of OPG autoantibodies were carried by radiobinding assays. Cut-off levels for a positive value were determined from the deviation from normality in the distribution of 398 healthy blood donors representing the 99.7th percentile. ResultsForty-five of the 698 (6.6%) women were IgG-OPG positive compared with 2 of 398 (0.5%) controls (p<0.0001) and 35 of the 698 (5.0%) women had a T-score<−2.5. There was no difference in bone mineral density between IgG-OPG positive (median 0.439 (range 0.315–0.547) g/cm2) women and IgG-OPG negative (median 0.435 (range 0.176–0.652) g/cm2) women (p=0.3956). Furthermore, there was neither a correlation between IgG-OPG levels and bone mineral density (rs=0.1896; p=0.2068) nor T-score (rs=0.1889; p=0.2086). Diagnostic sensitivity and specificity of IgG-OPG for low bone mineral density were 5.7% and 92.9%, and positive and negative predictive values were 7.4% and 90.8%, respectively. ConclusionElevated OPG autoantibody levels do not predict low bone mineral density in middle-aged women selected from the general population.

Comparison of Central and Peripheral Bone Mineral Density Measurements in Postmenopausal Women

ObjectivesThe purpose of the current study was to compare central and peripheral bone mineral density at different regions including spine, hip, and wrist in postmenopausal women. MethodsForty postmenopausal women participated in this study. Their mean age, body mass, height, and body mass index were 53.5 ± 2.75 y, 68.6 ± 8.68 kg, 167.8 ± 6.46 cm, and 24.31 ± 1.69 kg/m2, respectively. Bone mineral density (BMD) T-scores of spine, hip, and wrist regions were measured for all participants with a dual-energy X-ray absorptiometry scan. ResultsAll measured regions (spine, hip, and wrist) had low BMD T-scores. Bone mineral density of the wrist was significantly lower (–2.58 ± 2.18) than that of both spine (–1.79 ± 0.98) and hip (–1.69 ± 1.37). In addition, there were no statistically significant differences in BMD between the spine and hip. ConclusionsIn this group of postmenopausal women, wrist BMD decreased more than spine and hip BMD. Both spine and hip BMD decreased by nearly the same percentage in postmenopausal women. Peripheral sites may be more representative of osteoporosis than central sites. Trial Registration: PACTR201602001478123.

Wrist bone mineral density utility in diagnosing hip osteoporosis in postmenopausal women.

Osteoporosis is a common bone disease that increases with age. Wrist bone mineral density (BMD) has significant correlation with other skeletal sites and it could be used as a diagnostic method for osteoporosis. The purpose of this study was to evaluate the role of wrist BMD in diagnosing osteoporosis in postmenopausal women. In this cross-sectional study, 99 postmenopausal women with mean age of 57 ± 6.9 (range 50-76) years were evaluated. BMD of nondominant wrist, lumbar spine (L2-L4) and femur bone using a dual-energy X-ray absorptiometry (DXA) device as well as lateral lumbosacral X-ray for degenerative joint disease (DJD) evaluation were measured. Mean T-score of wrist was lower than hip and lumbar area. Osteopenia and osteoporosis were observed in 40.4% and 59.6% in the wrist, 38.4% and 24.2% in the hip and 36.4% and 49.5% in lumbar-spine BMD measurements, respectively. There was positive correlation between wrist BMD with hip BMD (r = 0.468,p < 0.001) and lumbar BMD (r = 0.322, p = 0.001). DJD due to lumbosacral X-ray was reported in 84 cases (84.8%) including mild DJD in 45 (53.5%), moderate DJD in 33 (39.3%) and severe DJD in 6 (7.2%). Our results showed that wrist BMD has better accuracy than lumbar BMD in diagnosing osteoporosis in postmenopausal women.

Home monitoring of bone density in the wrist—a parametric EIT computer modeling study

Goal. The purpose of this computer modeling study is to validate the feasibility of a home monitoring system for wrist bone mineral density (BMD) measurement which is based on the parametric electrical impedance tomography (pEIT) method. Methods. A solution to the forward problem of the developing potential around the wrist due to current injection was developed using a Matlab numerical simulation of an adult computer human phantom. The backward problem is solved by building a lookup table of different bone densities which represent different disease stages. Results. The real part of the complex potential exhibits an average change of 30.7%–12% (between the most sensitive and the least sensitive electrodes) per BMD decrease of 23%. A 2 times higher sensitivity to a deterioration of the cortical bone than of the trabecular bone alone was found. A signal to noise ratio (SNR) level above 30 dB is required for a maximal performance of the system. The robustness to a deposition of the electrodes array in different directions is limited. Conclusion. It was found that the cortical BMD changes govern the model. The required SNR level is within the specs of similar systems. In a real device, the issue of sensors repositioning should be addressed. The proposed pEIT system makes self-monitoring of wrist BMD possible. It brings an added-value by enabling the monitoring of BMD between treatments and between traditional DEXA screenings.

Effects of impact‐loaded sport training on bone bending stiffness and BMD in young females (706.16)

BLACKGROUND: Participation in high‐impact loading or odd‐impact loading sports is associated with higher bone mineral density (BMD) and bone mass. OBJECTIVE: The objective of this study is to compare the impact of sport training in long‐distance running, soccer and volleyball practice on BMD and bone bending strength in female athletes, 18‐24 years old.METHODS. 57 trained female athletes participated in this study. They were 22 soccer players (SOC), 22 long‐distance runners (RUN), and 13 volleyball players (VOL). Their ages were 19.1, 20.5 and 21.5 yr for the SOC, RUN and VOL, respectively. Sport training history was: 13, 11 and 10 yr for the SOC, RUN and VOL, respectively. Mean height, weight and BMI were 163 cm (±4.7), 59.8 kg (±4.1) and BMI 22.6 kg/m2 (±1.9), respectively. We also recruited 23 non‐athlete females, age 22.6 ± 0.5 yr, as control subjects. Bone bending stiffness was measured using a Mechanical Response Tissue Analyzer (MRTA, NASA‐ARC, CA), an in vivo technique expressed as EI in Nm2. EI was measured at the ulna and tibia. BMD was measured using a Duel‐Energy X‐ray Absorptiometry (PIXI‐DXA, in g/cm2) at two skeletal sites: heel and wrist.RESULTS. There are no differences in height, weight and BMI between the groups, except that VOL were significantly heavier and taller than the other groups. Tibia EI (TEI) of the RUN (122.7±89 Nm2) were significantly lower (p&lt;0.05) than VOL (228±89 Nm2), but not SOC (152±89 Nm2) and CON (85±89 Nm2). RUN has the lower ulnar EI (UEI=30.7±14 Nm2) relative to SOC (44±14 Nm2) and VOL (44±14 Nm2). VOL has significantly higher TEI (228.3±89 Nm2, p&lt;0.05) compared with SOC, RUN and CON. Heel and wrist BMD of the SOC and VOL are 7% to 9.5% higher (p&lt;0.05) than the RUN and CON.CONCLUSION. Volleyball training exhibited greatest osteogenic adaptation in tibial EI compared with RUN and CON, but not in ulnar EI or heel and wrist BMD. Distance running did not induce high osteogenic adaptation in the tibial EI or heel BMD. The mechanism for these changes in bone EI and BMD is unknown.

A follow-up association study of two genetic variants for bone mineral density variation in Caucasians

We tested whether two genetic variants were associated with BMD at multiple clinically relevant skeletal sites in Caucasians. We found that variant rs7776725 is consistently associated with hip, spine, wrist and whole-body BMD, which highlights the potential importance of this variant or linked variants for osteoporosis. A recent genome-wide association study identified two single nucleotide polymorphisms (SNPs), rs7776725 and rs1721400, that were associated with bone mineral density (BMD) variation at the radius, tibia and calcaneus in a Korean population. In this study, we aimed to test whether the association of these two genetic variants can be replicated in Caucasians and whether their association with BMD can be extended to other clinically relevant skeletal sites. We performed this study in two large cohorts of unrelated US Caucasians. Area BMD at the hip, spine, wrist (ultra-distal radius) and whole body were measured with Hologic dual-energy X-ray absorptiometer. SNPs were genotyped with Affymetrix human genome-wide genotyping arrays. Association analyses were performed using PLINK. We detected highly significant association (combined p = 1.42 × 10(-16)) of rs7776725 with wrist BMD but only borderline association signal (combined p = 0.017) for rs1721400 with wrist BMD. In addition, we found that rs7776725 was associated with BMD at the hip, spine and whole body. At the FAM3C gene locus where rs7776725 was located, we identified several other SNPs (rs4727922, rs1803389, rs718766 and rs7793554) that were also associated with BMD. This is the first follow-up association study of rs7776725 and rs1721400 with BMD. The rs7776725 showed consistent association with BMD at multiple clinically important skeletal sites, which highlighted the potential importance of rs7776725 or linked SNPs for risk of osteoporosis. Further in-depth re-sequencing studies and functional assays are necessary to elucidate the underlying mechanisms.

Association between Low Density Lipoprotein Receptor-Related Protein 2 Gene Polymorphisms and Bone Mineral Density Variation in Chinese Population

Low density lipoprotein receptor-related protein 2 gene (LRP2) is located next to the genomic region showing suggestive linkage with both hip and wrist bone mineral density (BMD) phenotypes. LRP2 knockout mice showed severe vitamin D deficiency and bone disease, indicating the involvement of LRP2 in the preservation of vitamin D metabolites and delivery of the precursor to the kidney for the generation of 1α,25(OH)2D3. In order to investigate the contribution of LRP2 gene polymorphisms to the variation of BMD in Chinese population, a total of 330 Chinese female-offspring nuclear families with 1088 individuals and 400 Chinese male-offspring nuclear families with 1215 individuals were genotyped at six tagSNPs of the LRP2 gene (rs2389557, rs2544381, rs7600336, rs10210408, rs2075252 and rs4667591). BMD values at the lumbar spine 1–4 (L1-4) and hip sites were measured by DXA. The association between LRP2 polymorphisms and BMD phenotypes was assessed by quantitative transmission disequilibrium tests (QTDTs) in female- and male-offspring nuclear families separately. In the female-offspring nuclear families, rs2075252 and haplotype GA of rs4667591 and rs2075252 were identified in the nominally significant total association with peak BMD at L1-4; however, no significant within-family association was found between peak BMD at the L1-4 and hip sites and six tagSNPs or haplotypes. In male-offspring nuclear families, neither the six tagSNPs nor the haplotypes was in total association or within-family association with the peak BMD variation at the L1-4 and hip sites by QTDT analysis. Our findings suggested that the polymorphisms of LRP2 gene is not a major factor that contributes to the peak BMD variation in Chinese population.

Efficacy of Teriparatide in Patients with Resolved Secondary Hyperparathyroidism due to Vitamin D Deficiency

To determine the efficacy of at least 1 year of teriparatide therapy on bone mineral density (BMD), T-scores, and rates of occurrence of fractures in patients with a history of resolved secondary hyperparathyroidism due to vitamin D deficiency and to compare its efficacy with that in patients without a history of resolved secondary hyperparathyroidism. In this retrospective study based on a search of electronic medical records, we collected the following data: patient demographics, doses of calcium and vitamin D supplementation, duration of teriparatide treatment, history and treatment of secondary hyperparathyroidism, BMD information, T-scores, and any history of fractures. Paired and unpaired t tests, the Fisher exact test, and the Wilcoxon rank sum test were used for statistical analysis. Ninety-five patients (7 with a history of resolved secondary hyperparathyroidism due to vitamin D deficiency and 88 without such a history) fulfilled the study inclusion criteria. Baseline characteristics (demographics, median calcium and vitamin D supplementation doses, mean BMD, mean T-scores, and fracture rates before teriparatide therapy) were similar between the 2 groups. In comparison with baseline data, after a mean of 21 months of teriparatide therapy: (1) hip BMD and T-scores did not change in either study group (with no significant differences between the 2 groups), (2) spine BMD and T-scores significantly improved in both study groups (with no significant differences between them), and (3) wrist T-scores significantly worsened in both study groups (with wrist BMD significantly lower in patients without a history of secondary hyperparathyroidism). No patients with a history of secondary hyperparathyroidism sustained a fracture while receiving teriparatide therapy versus 6 of 88 patients without a history of secondary hyperparathyroidism (P = .624). Patients with a history of resolved secondary hyperparathyroidism attributable to vitamin D deficiency responded to teriparatide therapy in a fashion similar to patients without such a history.

A genome-wide association analysis implicates SOX6 as a candidate gene for wrist bone mass

Osteoporosis is a highly heritable common bone disease leading to fractures that severely impair the life quality of patients. Wrist fractures caused by osteoporosis are largely due to the scarcity of wrist bone mass. Here we report the results of a genome-wide association study (GWAS) of wrist bone mineral density (BMD). We examined ∼500000 SNP markers in 1000 unrelated homogeneous Caucasian subjects and found a novel allelic association with wrist BMD at rs11023787 in the SOX6 (SRY (sex determining region Y)-box 6) gene (P=9.00×10(-5)). Subjects carrying the C allele of rs11023787 in SOX6 had significantly higher mean wrist BMD values than those with the T allele (0.485:0.462 g cm(-2) for C allele vs. T allele carriers). For validation, we performed SOX6 association for BMD in an independent Chinese sample and found that SNP rs11023787 was significantly associated with wrist BMD in the Chinese sample (P=6.41×10(-3)). Meta-analyses of the GWAS scan and the replication studies yielded P-values of 5.20×10(-6) for rs11023787. Results of this study, together with the functional relevance of SOX6 in cartilage formation, support the SOX6 gene as an important gene for BMD variation.

Pathway-based genome-wide association analysis identified the importance of regulation-of-autophagy pathway for ultradistal radius BMD

Wrist fracture is not only one of the most common osteoporotic fractures but also a predictor of future fractures at other sites. Wrist bone mineral density (BMD) is an important determinant of wrist fracture risk, with high heritability. Specific genes underlying wrist BMD variation are largely unknown. Most published genome-wide association studies (GWASs) have focused only on a few top-ranking single-nucleotide polymorphisms (SNPs)/genes and considered each of the identified SNPs/genes independently. To identify biologic pathways important to wrist BMD variation, we used a novel pathway-based analysis approach in our GWAS of wrist ultradistal radius (UD) BMD, examining approximately 500,000 SNPs genome-wide from 984 unrelated whites. A total of 963 biologic pathways/gene sets were analyzed. We identified the regulation-of-autophagy (ROA) pathway that achieved the most significant result (p = .005, qfdr = 0.043, pfwer = 0.016) for association with UD BMD. The ROA pathway also showed significant association with arm BMD in the Framingham Heart Study sample containing 2187 subjects, which further confirmed our findings in the discovery cohort. Earlier studies indicated that during endochondral ossification, autophagy occurs prior to apoptosis of hypertrophic chondrocytes, and it also has been shown that some genes in the ROA pathway (e.g., INFG) may play important roles in osteoblastogenesis or osteoclastogenesis. Our study supports the potential role of the ROA pathway in human wrist BMD variation and osteoporosis. Further functional evaluation of this pathway to determine the mechanism by which it regulates wrist BMD should be pursued to provide new insights into the pathogenesis of wrist osteoporosis. © 2010 American Society for Bone and Mineral Research.

Benchmark dose for cadmium-induced osteoporosis in women

We applied a hybrid approach to estimate the benchmark dose (BMD) and the lower 95% confidence limit (BMDL) for cadmium-induced bone effects in a population with low environmental exposure. Morning urine samples were collected by 794 Swedish women, aged 53–64 years, participating in a population-based study. We measured urinary cadmium (U-Cd), a marker of long-term exposure, and bone mineral density, expressed as its T-score (reference: 20-year old women) of the non-dominant wrist. BMD and BMDL, adjusted for relevant covariates, corresponding to an additional risk (BMR) of 5% or 10% were calculated, with the background risk at zero exposure set at 1% or 5%. With a BMR of 5% and a background risk of having low bone mineral density (at U-Cd = 0) of 1% or 5% (corresponding to T-score cut-offs −2.75 and −2.09, respectively), the BMD of U-Cd ranged 1.8–3.7 μg/g creatinine, and the BMDL ranged 1.0–2.1 μg/g creatinine. For a 5% BMR of osteoporosis ( T-score < −2.5), the BMD was 2.9 μg/g creatinine and the BMDL 1.6 μg/g creatinine. The lowest obtained BMD of U-Cd for wrist bone mineral density was only slightly higher than the lowest reference concentration previously reported for cadmium-related kidney effects. Our results provide additional scientific support for the low tolerably weekly intake (TWI) of cadmium set by the European Food Safety Authority in 2009.

Localization of Quantitative Trait Loci for Bone Mineral Density on Chromosome 13 in the Mongolian Population

Although the genetic basis for bone mineral density (BMD) has been studied by many groups so far, genes responsible for this complex trait has not been completely revealed. In order to localize quantitative trait loci (QTLs) for BMD variation in Asian population, the study was designed using a group of Mongolian population, a genetically closed population with a homogeneous lifestyle. BMD was measured at the left and right wrists and ankles using DEXA in 1,082 participants from 142 families. Genotyping of 13 polymorphic microsatellite markers on chromosome 13 (average spacing 8-9 cM) and two-point and multipoint linkage analysis were performed. In two-point linkage analysis, we identified two markers, D13S175 (6.03 cM) and D13S265 (68.73 cM) that had LOD scores greater than 1 for left ankle (LOD=2.09, LOD=1.49, respectively). We also found a marker D13S175 (6.03 cM) with a high LOD for left wrist (LOD=1.49) and the markers D13S265 (68.73 cM) and D13S217 (17.21 cM) for the right wrist (LOD= 1.82, LOD= 1.62, respectively). Among these significant marker regions, only two regions at 17 cM (13p11) and 65 cM (13q21) for the right wrist overlapped with major QTLs reported in following multipoint linkage analysis (LOD= 1.7549, LOD=1.4462, respectively). This study provides the possible evidence of the presence of QTLs affecting right wrist BMD in Mongolian populations on 13p11 and 13q21. Modest evidence was also found for genes affecting left ankle and left wrist BMD on 13p13.

Bone Bending Stiffness And Mineral Density In Endurance Cyclists, Runners And Untrained Men

Mechanical Tissue Response Analysis (MRTA) is a novel technique that may be used to non-invasively measure bone bending stiffness or EI (E is the modulus of elasticity and I, the bending moment of inertia), a measure of bone strength. PURPOSE: To examine the effects of running and cycling exercise in athletes on measurements of bone bending stiffness and bone mineral density (BMD). METHODS: Volunteers were 22 athletes (11 NCAA division II runners and 12 road race cyclists) for comparison with 12 untrained men (CON) of similar age (24.3±5.4 vs. 22.4±2.1 yrs). Left Ulnar and tibial bone bending stiffness (EI) were measured with the MRTA. A Peripheral Instantaneous X-ray Imager (PIXI, GE Lunar) was used to determine BMD of the left heel and wrist. All measured EI and BMD variables between the two athletic groups (ATH) were similar, except the heel BMD. The runners have higher heel BMD than the cyclists (0.6329±0.088 vs. 0.6651±0.078 g/cm2, p < .05). Thus, descriptive, MRTA and PIXI data were combined for the ATH compared to the CON. The means were subjected to a 2-tailed t-test for all measured variables with equal variances. RESULTS: The ATH were lighter in weight and in BMI than the CON (70.1±9.1 kg and 22.6±2.0 kg/m2 vs. 78.5±11.6 kg and 25.4±3.6 kg/m2, respectively, both p<0.05). The ATH have higher ulna EI (60.8±19.6 vs. 44.1±9.7 Nm2, p<0.01) and heel BMD than CON (.647±0.08 vs. 0.578±0.06 g/cm2, p<0.01). The ATH have almost similar tibial EI (322±101 vs. 274±74 Nm2) and wrist BMD values relative to the CON (0.553±0.065 vs. 0.526±0.062 g/cm2). The small sample size precluded detecting differences in the tibial EI and the wrist BMD measurements between the two athletic groups. CONCLUSION: The results show similar values for ulnar and tibial EI as well as wrist BMD in athletes engaged in different types of sports. Their ulna strength and heel BMD values were greater than values in the untrained controls. (Partially supported by -NASA grant No. SAA2-401535).