Ultradistal Radius Bone Mineral Density Research Articles

The Effects of a 1-Year Recreational Kung Fu Protocol on Bone Health Parameters in a Group of Healthy Inactive Young Men

The main aim of the current study was to explore the effects of a 1-year recreational Kung Fu protocol on bone health parameters (bone mineral content (BMC), bone mineral density (BMD), femoral neck geometry and composite indices of femoral neck strength) in a group of healthy inactive young men. 54 young inactive men voluntarily participated in this study, but only 51 of them completed it. The participants were assigned to 2 different groups: control group (n=31) and Kung Fu group (n=20). The Kung Fu group performed two sessions of recreational Kung Fu per week; the duration of each session was 45 minutes. The current study has demonstrated that whole body (WB) BMC, ultra-distal (UD) radius BMD, 1/3 radius BMD, total radius BMD, total forearm BMD, maximal strength, maximum oxygen consumption and jumping performance increased in the Kung Fu group but not in the control group. The percentages of variations in WB BMC, forearm BMD and physical performance parameters were significantly different between the two groups. In conclusion, this study suggests that recreational Kung Fu is an effective method to improve WB BMC, forearm BMD and physical performance parameters in young inactive men.

Bone mineral density of the ultra-distal radius: are we ignoring valuable information?

Bone mineral density (BMD) measurement of a non-dominant arm is not routinely performed during dual-X-ray-absorptiometry (DXA) test, and the possible utility of ultra-distal (UDR) radius BMD is not well-studied. We evaluated in women, correlations of UDR BMD with fracture prevalence, fracture risk prediction by the fracture risk assessment tool (FRAX), and osteoporosis diagnosed by traditional sites. Women who underwent a routine DXA (including their non-dominant forearm and including UDR BMD) in a tertiary medical center were included. Risk factors relevant to FRAX calculation were assessed via a self-administered questionnaire. Spearman correlations of UDR BMD to 10-year risks of major osteoporotic and hip fractures (assessed by FRAX) were explored. The possible added value of UDR BMD in explaining prevalent osteoporotic fractures was assessed using a multivariable regression model incorporating age and traditional osteoporosis diagnosis. The study included 1245 women with a median age of 66years (interquartile range: 59-73), of whom 298 (24%) had UDR T-score ≤ - 2.5 and 154 (12%) reported prior fractures. UDR BMD was significantly negatively correlated with FRAX risk score for hip and major osteoporotic fractures (R = - 0.5 and R = - 0.41, respectively; P < 0.001). UDR T-score ≤ - 2.5 was associated with higher fracture prevalence (19% vs 10%; P < 0.001) and remained significant after adjusting for traditional BMD and age (OR 1.49, 1.01-2.19; P = 0.043). UDR BMD correlates both with prior fractures and with predicted fracture risks and might pose added value over traditional DXA sites.

Risk factors for lower bone mineral density in older adults with type 1 diabetes: a cross-sectional study

Type 1 diabetes is associated with lower bone mineral density (BMD) and increased fracture risk, but little is known regarding the effects of diabetes-related factors on BMD. We assessed whether these factors are associated with lower hip BMD among older adults with type 1 diabetes. This cross-sectional study was embedded in a long-term observational study, the Epidemiology of Diabetes Interventions and Complications study (EDIC), a cohort of participants with type 1 diabetes, who were originally enrolled in the Diabetes Control and Complications Trial (DCCT), and were followed-up for more than 30 years at 27 sites in the USA and Canada. All active EDIC participants were eligible except if they were pregnant, weighed above the dual-energy x-ray absorptiometry (DXA) scanner limit, had an implanted neurostimulator, or were not willing to participate. The primary study outcome was total hip BMD. Hip, spine, and radius BMD and trabecular bone score (TBS) were measured with DXA at an annual EDIC visit (2017-19). Time-weighted mean HbA1c, kidney disease, and peripheral neuropathy were measured annually during EDIC, and retinopathy was measured every 4 years. Skin intrinsic fluorescence, a measure of advanced glycation end products (AGEs), and cardiac autonomic neuropathy were assessed once (2009-10) during EDIC. 1147 of the 1441 participants who were enrolled in the DCCT trial remained active EDIC participants at the start of this cross-sectional study. Between Sept 20, 2017, and Sept 19, 2019, 1094 of 1147 participants were screened for the EDIC Skeletal Health study. 1058 participants completed at least one of a set of DXA scans and were included in the analysis. 47·8% were women and 52·2% were men, 96·6% were White and 3·4% were of other race or ethnicity. The mean age of participants was 59·2 years (SD 6·7). Higher mean HbA1c, higher skin intrinsic fluorescence, and kidney disease (but not retinopathy or neuropathy) were independently associated with a lower total hip BMD. Total hip BMD differed by -10·7 mg/cm2 (95% CI -19·6 to -1·7) for each 1% increase in mean HbA1c, -20·5 mg/cm2 (-29·9 to -11·0) for each 5 unit higher skin intrinsic fluorescence, and -51·7 mg/cm2 (-80·6 to -22·7) in the presence of kidney disease. Similar associations were found for femoral neck and ultra-distal radius BMD, but not for lumbar spine BMD or TBS. Poorer glycaemic control, AGE accumulation, and kidney disease are independent risk factors for lower hip BMD in older adults with type 1 diabetes. Maintenance of glycaemic control and prevention of kidney disease might reduce bone loss and ultimately fractures in this population. Osteoporosis screening might be particularly important in people with these risk factors. Further research to identify AGE blockers could benefit skeletal health. National Institute of Diabetes and Digestive and Kidney Disease.

Associations of pregnancy phthalate concentrations and their mixture with early adolescent bone mineral content and density: The Health Outcomes and Measures of the Environment (HOME) study.

The developing fetus may be particularly susceptibility to environmental osteotoxicants, but studies of pregnancy phthalate exposures and childhood bone health are scarce. To examine relations of pregnancy phthalate exposure biomarkers with early adolescent bone mineral density (BMD) and bone mineral content (BMC) in a prospective birth cohort. We used data from 223 pregnant mothers and their children enrolled in a Cincinnati, OH area cohort from 2003 to 2006. We quantified monoethyl phthalate (MEP), monoisobutyl phthalate, monobutyl phthalate, monobenzyl phthalate, mono-(3-carboxypropyl) phthalate (MCPP), and four metabolites of di-2-ethylhexyl phthalate in maternal urine collected at 16 and 26weeks gestation, and calculated the average of creatinine-standardized concentrations. Using dual x-ray absorptiometry measures at age 12years, we calculated BMD and BMC Z-scores for six skeletal sites. In overall and sex-stratified models, we estimated covariate-adjusted associations per 2-fold increase in phthalate biomarker concentrations using linear regression, and estimated joint effects of the phthalate biomarkers mixture using Bayesian kernel machine regression (BKMR) and quantile g-computation. In single phthalate models, several biomarkers were positively associated with BMC and BMD. For example, each doubling of MEP and MCPP, 1/3rd distal radius BMD Z-score increased by 0.09 (95% CI: 0.01, 0.17) and 0.16 (95% CI: 0.01, 0.31), respectively. For phthalate mixtures, associations were generally U-shaped among males and positive-linear among females, using both statistical methods. Mixture associations were strongest with forearm sites: in BKMR models, increasing all biomarkers from the 50th to 90th percentile was associated with a 0.64 (95% CI: 0.01, 1.28) greater 1/3rd distal radius BMD Z-score in males, and a 0.49 (95% CI: -0.13, 1.10) greater ultradistal radius BMD Z-score in females. In this study, phthalate exposures during gestation were associated with increased BMD Z-scores in early adolescence, though further research is needed to determine implications for long-term skeletal health.

Deficits in the Functional Muscle–Bone Unit in Youths with Fontan Physiology

To determine whether dual energy X-ray absorptiometry (DXA), a clinically available tool, mirrors the magnitude of deficits in trabecular and cortical bone mineral density (BMD) demonstrated on peripheral quantitative computed tomography in youth with Fontan physiology. We aimed to describe DXA-derived BMD at multiple sites and to investigate the relationship between BMD and leg lean mass, a surrogate for skeletal muscle loading. Subjects with Fontan (n=46; aged 5-20years) underwent DXA in a cross-sectional study of growth and bone and muscle health as described previously. Data from the Bone Mineral Density in Childhood Study were used to calculate age-, sex-, and race-specific BMD z-scores of the whole body, lumbar spine, hip, femoral neck, distal one-third radius, ultradistal radius, and leg lean mass z-score (LLMZ). Fontan BMD z-scores were significantly lower than reference at all sites-whole body, -0.34±0.85 (P=.01); spine, -0.41±0.96 (P=.008); hip, -0.75±1.1 (P<.001); femoral neck, -0.73±1.0 (P<.001); distal one-third radius, -0.87±1.1 (P<.001); and ultradistal radius. -0.92±1.03 (P<.001)-as was LLMZ (-0.93±1.1; P<.001). Lower LLMZ was associated with lower BMD of the whole body (R2=0.40; P<.001), lumbar spine (R2=0.16; P=.005), total hip (R2=0.32; P<.001), femoral neck (R2=0.47; P<.001), and ultradistal radius (R2=0.35; P<.001). Patients with Fontan have marked deficits in both cortical (hip, distal one-third radius) and trabecular (lumbar spine, femoral neck, ultradistal radius) BMD. Lower LLMZ is associated with lower BMD and may reflect inadequate skeletal muscle loading. Interventions to increase muscle mass may improve bone accrual.

Forearm bone mineral density and fracture incidence in postmenopausal women with osteoporosis: results from the ACTIVExtend phase 3 trial

SummaryAbaloparatide increased ultradistal radius bone mineral density (BMD) in the Abaloparatide Comparator Trial in Vertebral Endpoints (ACTIVE) trial. Over the subsequent 24 months in ACTIVExtend, ultradistal radius BMD gains were maintained with alendronate. Conversely, 1/3 radius BMD remained stable during ALN treatment in ACTIVExtend after decreasing during ACTIVE.IntroductionAbaloparatide (ABL) increased femoral neck, total hip, and lumbar spine bone mineral density (BMD) in postmenopausal women with osteoporosis and decreased the risk of vertebral and nonvertebral fractures in ACTIVE. Effects on fracture risk and BMD were maintained subsequently with alendronate (ALN) in ACTIVExtend. In a prespecified subanalysis of ACTIVE, ABL also increased BMD at the ultradistal radius. Our objective was to determine the efficacy of ABL followed by ALN vs placebo (PBO) followed by ALN on forearm BMD and fracture risk over 43 months in ACTIVExtend.MethodsUltradistal and 1/3 radius BMD (ACTIVE baseline to month 43) were measured (ABL/ALN, n = 213; PBO/ALN, n = 233). Wrist fracture rates were estimated for the ACTIVExtend intent-to-treat population (ABL/ALN, n = 558; PBO/ALN, n = 581) by Kaplan-Meier (KM) method.ResultsAt cumulative month 25, mean increase from ACTIVE baseline in ultradistal radius BMD was 1.1% (standard error, 0.49%) with ABL/ALN vs − 0.8% (0.43%) with PBO/ALN (P < 0.01). BMD increases with ABL were maintained with ALN through month 43 in ACTIVExtend. BMD decreases at the 1/3 radius in ACTIVE (similar with ABL and PBO) were maintained through 24 months of ALN treatment in ACTIVExtend. Wrist fractures over 43 months occurred in 15 women with ABL/ALN (KM estimate, 2.8%) and 20 with PBO/ALN (KM estimate, 3.6%) (HR = 0.77, 95% CI 0.39, 1.50; P = not significant).ConclusionUltradistal radius BMD gains following treatment with ABL in ACTIVE were maintained over 24 months of ALN treatment in ACTIVExtend. Conversely, 1/3 radius BMD remained stable during ALN treatment in ACTIVExtend after decreasing during ACTIVE.Trial registrationClinicalTrials.gov: NCT01657162 submitted July 31, 2012

Impact of reference point selection on DXA-based measurement of forearm bone mineral density.

Forearm fractures are clinically important outcomes from the perspective of morbidity, health care costs, and interruption of work. BMD of the forearm, as derived by dual-energy x-ray absorptiometry (DXA), is a better predictor of fracture at the forearm compared with BMD measured at other sites. However, very few studies have evaluated the technical aspects of selecting the ROI for forearm BMD measurement. This study aimed to compare the BMD values measured at the 1/3 radius site using three different reference points: the ulnar styloid process, the radial endplate, and the bifurcation of the ulna and radius. Healthy Chinese patients participating in the control group of an ongoing study at Zhejiang Provincial People's Hospital were recruited for this study. For each patient, a DXA scan (GE Lunar Prodigy) of the forearm was performed and BMD values were separately calculated using each of the three reference points to identify the ROI. Pearson correlation coefficients were calculated to examine the correlation between the BMD measures derived from each reference point. The F test and independent t test were applied for more robust analysis of the differences in the variances and means. Sixty-eight healthy Chinese volunteers agreed to participate in this study. The root mean square standard deviation (RMS-SD) percentages of BMD values measured at the 1/3 radius site were 2.19%, 2.23%, and 2.20% when using the ulnar styloid process, radial endplate, and the bifurcation of the ulna and radius as the reference points, respectively. Pearson's correlation coefficients for all pairwise comparisons among these three groups were greater than 0.99. F tests and independent t tests showed p values ranging from 0.92 to 0.99. However, we observed that among 10% of patients, choosing an ROI at the ulnar styloid process led to an inability to accurately determine the BMD at the ultra-distal radius. Given equal ability to determine BMD at the 1/3 radius accurately, the radial endplate or the bifurcation of the ulna and radius should be preferentially selected as the reference point for routine forearm BMD measurements in order to avoid situations in which the ultra-distal radius BMD cannot be determined.

Abaloparatide effect on forearm bone mineral density and wrist fracture risk in postmenopausal women with osteoporosis

PurposeWrist fractures are common, contribute significantly to morbidity in women with postmenopausal osteoporosis, and occur predominantly at the ultradistal radius, a site rich in trabecular bone. This exploratory analysis of the phase 3 ACTIVE study evaluated effects of abaloparatide versus placebo and teriparatide on forearm bone mineral density (BMD) and risk of wrist fracture.MethodsForearm BMD was measured by dual energy X-ray absorptiometry in a subset of 982 women from ACTIVE, evenly distributed across the three treatment groups. Wrist fractures were ascertained in the total cohort (N = 2463).ResultsAfter 18 months, ultradistal radius BMD changes from baseline were 2.25 percentage points greater for abaloparatide compared with placebo (95% confidence interval (CI) 1.38, 3.12, p < 0.001) and 1.54 percentage points greater for abaloparatide compared with teriparatide (95% CI 0.64, 2.45, p < 0.001). At 18 months, 1/3 radius BMD losses (versus baseline) were similar for abaloparatide compared with placebo (−0.42; 95% CI −1.03, 0.20; p = 0.19) but losses with teriparatide exceeded those of placebo (−1.66%; 95% CI −2.27, −1.06; p < 0.001). The decline with abaloparatide was less than that seen with teriparatide (group difference 1.22%; 95% CI 0.57, 1.87; p < 0.001). The radius BMD findings, at both ultradistal and 1/3 sites, are consistent with the numerically lower incidence of wrist fractures observed in women treated with abaloparatide compared with teriparatide (HR = 0.43; 95% CI 0.18, 1.03; p = 0.052) and placebo (HR = 0.49, 95% CI 0.20, 1.19, p = 0.11).ConclusionsCompared with teriparatide, abaloparatide increased BMD at the ultradistal radius (primarily trabecular bone) and decreased BMD to a lesser extent at the 1/3 radius (primarily cortical bone), likely contributing to the numerically lower wrist fracture incidence observed with abaloparatide.

EFFECT OF POSITIONING OF THE ROI ON BMD OF THE FOREARM AND ITS SUBREGIONS

Inconsistent positioning of patients and region of interest (ROI) is known to influence the precision of bone mineral density (BMD) measurements in the spine and hip. However it is unknown whether minor shifts in the positioning of the ROI along the shaft of the radius affect the measurement of forearm BMD and its subregions. The ultradistal (UD), mid-, one-third (1/3), and total radius BMDs of 50 consecutive clinical densitometry patients were acquired. At baseline the distal end of the ROI was placed at the tip of the ulnar styloid as usual, and then the forearm was reanalyzed 10 more times, each time shifting the ROI 1 mm proximally. The data were normally distributed, and mean values at the various distances from baseline were compared using a paired t-test. No corrections for multiple comparisons were necessary since the differences that were significant were significant at p<0.0001. The UD forearm BMD increased as the ROI was shifted proximally; the increase was significant when shifted even 1 mm proximally (Figure 1a, p<0.0001). These same findings held true for the mid- and total radius bone density, though the percent increase with moving proximally was significantly greater for the UD radius than for the other subregions. However, there was no significant change in the 1/3 radius BMD when shifted proximally 1-10 mm (Figure 1b). Since the one-third radius is the only forearm region usually reported, proximal shifts of the ROI of up to 10 mm should not influence forearm BMD results significantly.

Effect of Positioning of the ROI on BMD of the Forearm and Its Subregions

Inconsistent positioning of patients and region of interest (ROI) is known to influence the precision of bone mineral density (BMD) measurements in the spine and hip. However, it is unknown whether minor shifts in the positioning of the ROI along the shaft of the radius affect the measurement of forearm BMD and its subregions. The ultradistal (UD-), mid-, one-third, and total radius BMDs of 50 consecutive clinical densitometry patients were acquired. At baseline the distal end of the ROI was placed at the tip of the ulnar styloid as usual, and then the forearm was reanalyzed 10 more times, each time shifting the ROI 1 mm proximally. No corrections for multiple comparisons were necessary since the differences that were significant were significant at p < 0.001. The UD-radius BMD increased as the ROI was shifted proximally; the increase was significant when shifted even 1 mm proximally (p < 0.001). These same findings held true for the mid- and total radius bone density, though the percent increase with moving proximally was significantly greater for the UD radius than for the other subregions. However, there was no significant change in the one-third radius BMD when shifted proximally 1–10 mm. Minor proximal shifts of the forearm ROI substantially affect the BMD of the UD-, mid- and total radius, while having no effect on the one-third radius BMD. Since the one-third radius is the only forearm region usually reported, minor proximal shifts of the ROI should not influence forearm BMD results significantly.

Treatment with neridronate in children and adolescents with osteogenesis imperfecta: Data from open-label, not controlled, three-year Italian study

IntroductionThe present study assessed the long-term efficacy and safety of intravenous (i.v.) neridronate in children and adolescents affected by osteogenesis imperfecta (OI). Methods55 young patients (mean age 12.6±3.9years) affected by OI were included in the study. Neridronate was administered by i.v. infusion at a dose of 2mg/kg (maximum dose of 100mg) at intervals of three-months for three years. Dual X-ray absorptiometry of the lumbar spine, hip and ultradistal and proximal radius were evaluated every 6months. Blood calcium, phosphate, albumin, fasting urinary calcium/creatinine ratio were obtained at baseline and every 3months. Serum bone turnover markers total and bone alkaline phosphatase were performed every 12months in a proportion of patients. ResultsMean lumbar spine and total hip bone mineral density (BMD) and bone mineral content significantly increased from baseline compared to all subsequent time points (p<0.001). Mean ultradistal radius BMD significantly increased from month 18 (p=0.026). Levels of bone turnover markers significantly decreased from baseline to all post-baseline observation time points. There was no statistically significant effect on fracture risk (p=0.185), although a significant reduction was observed in the mean number of fractures occurring during treatment compared to pre-treatment values. The most frequent adverse events were arthralgia, fever, joint sprain. An acute phase reaction was reported in 26 (22.8%) patients. None of the reported serious adverse events was considered as treatment-related. ConclusionLong-term i.v. neridronate treatment has positive effects on BMD, bone turnover markers and fracture risk with a good safety profile.

Spine Trabecular Bone Score as an Indicator of Bone Microarchitecture at the Peripheral Skeleton in Kidney Transplant Recipients.

Studies using high-resolution peripheral quantitative computed tomography showed progressive abnormalities in cortical and trabecular microarchitecture and biomechanical competence over the first year after kidney transplantation. However, high-resolution peripheral computed tomography is a research tool lacking wide availability. In contrast, the trabecular bone score is a novel and widely available tool that uses gray-scale variograms of the spine image from dual-energy x-ray absorptiometry to assess trabecular quality. There are no studies assessing whether trabecular bone score characterizes bone quality in kidney transplant recipients. Between 2009 and 2010, we conducted a study to assess changes in peripheral skeletal microarchitecture, measured by high-resolution peripheral computed tomography, during the first year after transplantation in 47 patients managed with early corticosteroid-withdrawal immunosuppression. All adult first-time transplant candidates were eligible. Patients underwent imaging with high-resolution peripheral computed tomography and dual-energy x-ray absorptiometry pretransplantation and 3, 6, and 12 months post-transplantation. We now test if, during the first year after transplantation, trabecular bone score assesses the evolution of bone microarchitecture and biomechanical competence as determined by high-resolution peripheral computed tomography. At baseline and follow-up, among the 72% and 78%, respectively, of patients having normal bone mineral density by dual-energy x-ray absorptiometry, 53% and 50%, respectively, were classified by trabecular bone score as having high fracture risk. At baseline, trabecular bone score correlated with spine, hip, and ultradistal radius bone mineral density by dual-energy x-ray absorptiometry and cortical area, density, thickness, and porosity; trabecular density, thickness, separation, and heterogeneity; and stiffness and failure load by high-resolution peripheral computed tomography. Longitudinally, each percentage increase in trabecular bone score was associated with increases in trabecular number (0.35%±1.4%); decreases in trabecular thickness (-0.45%±0.15%), separation (-0.40%±0.15%), and network heterogeneity (-0.48%±0.20%); and increases in failure load (0.22%±0.09%) by high-resolution peripheral computed tomography (all P<0.05). Trabecular bone score may be a useful method to assess and monitor bone quality and strength and classify fracture risk in kidney transplant recipients.

Unilateral Ön Kol Vibrasyonu Uygulanan Olgularda Radius Kemik Yoğunluğunun Kontralateral El Bilek Fleksör İstirahat Kas Elektriksel Aktivitesi Üzerine Etkisi

Objective: To investigate whether bone mineral density or bone mineral content of the ultradistal radius has any effect on the resting muscle activity of contralateral wrist flexor muscles during unilateral forearm vibration. Material and Methods: Ninety healthy adult volunteers (33 women, 57 men) were included in this study. The mean age of participants was 34.2 (20-52) years. The right forearm was exposed to vibration for 1 minute. The frequency of vibration was 46 Hz. The resting myoelectrical activities of the right and left wrist flexor muscles were simultaneously measured by surface electromyography before, during and after vibration. The right ultradistal radius bone mineral density and bone mineral content were measured by dual-energy X-ray absorbtiometry. Results: The resting myoelectrical activity of the left wrist flexor muscles significantly increased during vibration (from 2.0±0.8 microvolts to 4.5±2.2 microvolts, p=0.0001). It decreased to 1.8±0.9 microvolts after vibration (p=0.0001). Multiple linear regression analysis revealed that the right ultradistal radius bone mineral density was an independent predictor of the resting myoelectrical activity of the left wrist flexor muscles measured during vibration. However, age, gender, body mass index, the right ultradistal radius bone mineral content and, the right and left wrist flexor muscles' resting myoelectrical activity measured before vibration were not predictors (R2=0.772, F=301.8, p = 0.0001). Conclusion: It is suggested that the ultradistal radius bone may affect the resting myoelectrical activities in the contralateral wrist flexor muscles, based on its bone mineral density during unilateral forearm vibration.

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.

Bone mineral density analysis in patients with primary hyperparathyroidism associated with multiple endocrine neoplasia type 1 after total parathyroidectomy

Limited data have been reported on the effect of parathyroidectomy (PTx) on bone mineral density (BMD) in the setting of patients with hyperparathyroidism (HPT) associated with multiple endocrine neoplasia type 1 (MEN1). This study investigates the impact of total PTx on BMD in patients with HPT/MEN1. A case series study was performed in a tertiary academic hospital. A total of 16 HPT/MEN1 patients from six families harbouring MEN1 germline mutations were subjected to total PTx followed by parathyroid auto-implant in the forearm. Bone mineral density values were assessed using dual-energy X-ray absorptiometry. Before PTx, reduced BMD (Z-score <-2.0) was highly prevalent in the proximal one-third of the distal radius (1/3 DR) (50%), lumbar spine (LS) (43.7%), ultradistal radius (UDR) (43.7%), femoral neck (FN) (25%) and total femur (TF) (18.7%) in the patients. Fifteen months after PTx, we observed a BMD improvement in the LS (from 0.843 to 0.909 g/cm(2); +8.4%, P = 0.001), FN (from 0.745 to 0.798 g/cm(2); +7.7%, P = 0.0001) and TF (from 0.818 to 0.874 g/cm(2); +6.9%, P < 0.0001). No significant change was noticed in the 1/3 DR and UDR after PTx. This data confirmed BMD recovery in the LS and FN after PTx in HPT/MEN1 patients. We also documented a significant BMD increase in the TF and no change in both the 1/3 DR and UDR BMD after PTx. Our data suggest that LS and proximal femur are the most informative sites to evaluate the short-term BMD outcome after PTx in HPT/MEN1 subjects.

Habitual Site-Specific Upper Extremity Loading is Associated with Increased Bone Mineral of the Ultradistal Radius in Young Women

Osteoporosis and osteopenia are major contributors to the high incidence of fractures in older women. Habitual loading plays a crucial role in the acquisition and maintenance of bone. It may be possible to develop clinical interventions based on targeted modes of physical loading that can improve bone health and reduce fractures in women. If so, an important first step is determining the degree to which common fracture sites, such as the distal radius are responsive to habitual loading. The bone mineral density (BMD) and bone mineral content (BMC) of the ultradistal radius of 15 female gymnasts were compared with those of an age-matched, mass-matched, and height-matched control group. The hypothesis that the ultradistal radius BMD and BMC in gymnasts would be higher than those of the control group was tested using a 2 x 2 (left/right x group) repeated measures analysis of variance (MANOVA). After adjusting for the between-group difference in the influence of body mass, the gymnasts had 24% larger BMD and a 34% larger BMC at the ultradistal radii than the control group (p < 0.001). These results suggest that the ultradistal radius is responsive to the types and magnitudes of load encountered during gymnastics. A responsive distal radius is a necessary prerequisite to the development of loading-based interventions to increase ultradistal radius bone quality. Such interventions have the potential to significantly increase distal radius strength, thereby reducing the incidence of fracture.

Serum 1-84 and 7-84 parathyroid hormone concentrations and bone in patients with primary hyperparathyroidism

Parathyroid hormone (PTH) acts on bone as both anabolic and catabolic factor. It includes two fractions: 1-84 (cyclase activating PTH, CAP) which increases bone turnover and serum calcium, and 7-84 (cyclase inactivating PTH, CIP) acting the opposite way. The aim of this study was to establish whether bone mineral density (BMD) and turnover in patients' primary hyperparathyroidism (HPT) are dependent on CAP and CIP concentrations. Thirty-one patients with HPT and 29 appropriately matched controls were examined. Parameters of calcium-phosphate homeostasis and BMD were estimated. BMD of radius shaft was lower in patients with HPT as compared with controls, whereas BMD of spine and ultradistal radius were similar. Serum calcium, bone alkaline phosphatase, total PTH, 1-84 PTH, and 7-84 PTH were higher in HPT patients, whereas serum phosphate was lower and beta cross-laps similar. Both total PTH and CAP correlated significantly with BMD of radius shaft and serum calcium concentration, but not with other examined parameters. Total and 1-84 PTH are similarly associated with examined parameters in patients with HPT. Thus, determination of serum CAP concentration does not seem to have advantages over total PTH with regard to bone mineral density and bone turnover assessment in those patients.

Correlations between serum testosterone, estradiol, and sex hormone-binding globulin and bone mineral density in a diverse sample of men.

The relationship between hormones and bone mineral density (BMD) in men has received considerable attention. However, most studies have been conducted in homogenous populations, and it is not known whether differences in hormones impact racial and ethnic differences in BMD. Our objective was to examine associations of testosterone, estradiol, and sex hormone-binding globulin (SHBG) with BMD in a racially and ethnically diverse population. This was a population-based, observational survey. A total of 976 Black, Hispanic, and white randomly selected men ages 30-79 yr from the Boston Area Community Health/Bone Survey were included. BMD at the hip, wrist, and spine were calculated. The mean age of the sample was 46.7 +/- 12.4 yr. BMD levels were highest in black men, followed by Hispanic and then white men. Associations between hormones and BMD were consistent across racial and ethnic groups. Total and free testosterone was not correlated with BMD in age- or multivariate-adjusted models. SHBG was inversely correlated with total hip and ultradistal radius BMD after age adjustment, but not with multivariate adjustment for age, lean mass, fat mass, physical activity, self-rated health, and smoking. Total and free estradiol levels were positively and significantly correlated with femoral neck and total hip BMD, even with multivariate adjustment (partial correlations ranged between 0.11 and 0.16). However, estradiol levels failed to account for racial and ethnic differences in hip BMD. In our diverse population, neither serum total nor free testosterone levels were associated with BMD. Correlations between BMD and estradiol were significant but did not appear to account for any of the observed racial and ethnic differences in BMD. These findings suggest that differences in hormone levels are not a major contributor to the observed differences in BMD between Black, Hispanic, and white men.

The skeletal benefits of calcium- and vitamin D3–fortified milk are sustained in older men after withdrawal of supplementation: an 18-mo follow-up study

Background: In a previous 2-y randomized controlled trial, we showed that calcium- and vitamin D3–fortified milk stopped or slowed bone loss at several clinically relevant skeletal sites in older men.Objective: The present study aimed to determine whether the skeletal benefits of the fortified milk were sustained after withdrawal of the supplementation.Design: One hundred nine men >50 y old who had completed a 2-y fortified milk trial were followed for an additional 18 mo, during which no fortified milk was provided. Bone mineral density (BMD) of the total hip, femoral neck, lumbar spine, and forearm was measured by using dual-energy X-ray absorptiometry.Results: Comparison of the mean changes from baseline between the groups (adjusted for baseline age, BMD, total calcium intake, and change in weight) showed that the net beneficial effects of fortified milk on femoral neck and ultradistal radius BMD at the end of the intervention (1.8% and 1.5%, respectively; P < 0.01 for both) were sustained at 18-mo follow-up (P < 0.05 for both). The nonsignificant between-group differences at the total hip (0.8%; P = 0.17) also persisted at follow-up (0.7%; P = 0.10), but there were no lasting benefits at the lumbar spine. The average total dietary calcium intake in the milk supplementation group at follow-up approximated recommended amounts for Australian men >50 y old (1000 mg/d) but did not differ significantly from that in the control subjects (1021 versus 890 mg/d).Conclusion: Supplementation with calcium- and vitamin D3–fortified milk for 2 y may provide some sustained benefits for BMD in older men after withdrawal of supplementation.

Serum Levels of Insulin-Like Growth Factor (IGF); IGF-Binding Proteins-3, -4, and -5; and Their Relationships to Bone Mineral Density and the Risk of Vertebral Fractures in Postmenopausal Women

We previously found that serum levels of insulin-like growth factor I (IGF-I) and IGF-binding protein (IGFBP)-3, but not IFGBP-2, were associated with bone mineral density (BMD) and the risk of vertebral fractures. The aim of the present study was to investigate the roles of IGFBP-4 and -5 in age-dependent bone loss and vertebral fracture risk in postmenopausal Japanese women and to compare them with those of IGF-I and IGFBP-3. One hundred and ninety-three Japanese women aged 46-88 years (mean 62.5) were enrolled in the cross-sectional study. BMD was measured at the lumbar spine, femoral neck, ultradistal radius (UDR), and total body by dual-energy X-ray absorptiometry. Serum levels of IGFBP-4 and -5 as well as IGF-I and IGFBP-3 were measured by radioimmunoassay. Serum levels of IGF-I, IGFBP-3, and IGFBP-5 declined with age, while serum IGFBP-4 increased with age. Multiple regression analysis was performed between BMD at each skeletal site and serum levels of IGF-I and IGFBPs adjusted for age, body weight, height, and serum creatinine. BMD at the UDR was significantly and positively correlated with all serum levels of IGF-I and IGFBPs measured (P < 0.01), while BMD at the femoral neck was correlated with none of them. Serum IGF-I level was significantly and positively correlated with BMD at all sites except the femoral neck (P < 0.01), while serum IGFBP-3 and -4 levels were significantly and positively correlated with only radial BMD (P < 0.01). Serum IGFBP-5 level was positively correlated with UDR BMD (P < 0.001) and negatively correlated with total BMD (P < 0.05). Serum IGF-I, IGFBP-3, and IFGBP-5 levels were significantly lower in women with vertebral fractures than in those without fractures (mean +/- SD: 97.1 +/- 32.1 vs. 143.9 +/- 40.9 ng/dl, P < 0.0001; 2.18 +/- 1.02 vs. 3.23 +/- 1.07 microg/ml, P < 0.0001; 223.6 +/- 63.3 vs. 246.5 +/- 71.5 ng/ml, P = 0.0330, respectively). When multivariate logistic regression analysis was performed with the presence of vertebral fractures as a dependent variable and serum levels of IGF-I and IGFBPs adjusted for age, body weight, height, serum creatinine, and serum alubumin as independent variables, IGF-I and IGFBP-3 were selected as indices affecting the presence of vertebral fractures [odds ratio (OR) = 0.29, 95% confidential interval (CI) 0.15-0.57 per SD increase, P = 0.0003 and OR = 0.31, 95% CI 0.16-0.61 per SD increase, P = 0.0007, respectively]. To compare the significance values, IGF-I, IGFBP-3, and age were simultaneously added as independent variables in the analysis. IGFBP-3 was more strongly associated with the presence of vertebral fractures than IGF-I and age (P = 0.0006, P = 0.0148, and P = 0.0013, respectively). Thus, after comprehensive measurements of serum levels of IGF-I and IGFBPs, it seems that serum IGF-I level is most efficiently associated with bone mass and that serum IGFBP-3 level is most strongly associated with the presence of vertebral fractures in postmenopausal women among the IGF system components examined.