Distal Radius Bone Mineral Density Research Articles

Relationship between gut microbiome and bone deficits in primary hyperparathyroidism: A proof-of-concept pilot study.

Parathyroid hormone (PTH) interacts with components of the gut microbiota to exert its bone-regulating effects. This study aimed to investigate the gut microbial composition in patients with primary hyperparathyroidism (PHPT). Nine patients with PHPT and nine age-sex and body mass index-matched healthy controls were included. Gut microbial composition was assessed using 16S rRNA gene amplicon sequencing in both groups at baseline and 1 month after parathyroidectomy in the PHPT group. Data were imported into QIIME-2 and both QIIME-2 and R packages were used for microbiome analysis. Alpha and beta diversities were similar between the groups and remained unchanged after parathyroidectomy. The relative abundance of Subdoligranulum was significantly higher, whereas Ruminococcus, Alloprevotella, Phascolarctobacterium, and Clostridium sensu stricto_1 were significantly lower in PHPT than in controls (p < 0.001). After parathyroidectomy, the relative abundance of Subdoligranulum decreased, and Ruminococcus and Alloprevotella increased (p < 0.001). The PHPT group had lower total femoral and lumbar bone mineral density (BMD) than the controls (p < 0.05). At baseline, Alloprevotella abundance was positively correlated with serum phosphorus and Subdoligranulum was positively correlated with total lumbar BMD. Clostridium sensu stricto_1 was negatively correlated with serum calcium and positively correlated with femoral neck BMD. Postoperatively, Alloprevotella was positively correlated with baseline serum phosphorus and Phascolarctobacterium was positively correlated with distal radius BMD. This study demonstrated that the diversity of the gut microbiome was altered, possibly in response to electrolyte changes in PHPT, both before and after parathyroidectomy.

Increase in lumbar spine but not distal radius bone mineral density in adults after pancreas kidney transplantation

Osteoporosis occurs in every third individual after simultaneous pancreas kidney transplantation (SPKT). Currently used bone measures insufficiently predict their fracture risk. Lumbar spine Trabecular bone score (TBS) and distal radius areal and volumetric bone mineral density (BMD) were monitored for the first time in patients with type 1 diabetes and chronic renal failure after SPKT with steroid-sparing protocol. In 33 subjects (mean age 43.4 ± 9.8 years), dual-energy X-ray absorptiometry and peripheral quantitative computed tomography were performed just after SPKT (baseline) and one and three years later. While TBS Z-scores increased (−1.1 ± 1.2 and −0.3 ± 1.0; p˂0.001, at baseline and year three, respectively), trabecular volumetric BMD Z-scores at distal radius metaphysis did not change during the study (−1.3 ± 1.3 and −1.3 ± 1.0; p = 0.38). Similarly, areal BMD Z-scores increased at lumbar spine, total hip and femoral neck (all p < 0.01), but not at the distal radius. SPKT induced bone measures' improvement at lumbar spine and hip but not at distal radius. Before suggesting changes in current clinical care, predictive value of individual bone measures or its combination for fracture risk assessment remains to be elucidated.

Differences in dietary intake in early postmenopausal women with different levels of areal and volumetric bone mineral density: a cross-sectional analysis of baseline data from an intervention study

Osteoporosis is a degenerative disease of the bone. The rate of bone loss is accelerated during the first postmenopausal years in women which results in their disproportionate prevalence of osteoporosis(2). Some of the factors contributing to the development and maintenance of bone mineral density (BMD) relate to diet, particularly the intake of protein, calcium and other micronutrients that play a crucial role in bone composition(3). The most common method of measuring BMD is dual-energy X-ray absorptiometry (DXA) which generates a two-dimensional image of the scan site (typically spine, hip and/or forearm) to determine areal BMD (aBMD). However, new methods have recently emerged, including High Resolution peripheral Quantitative Computed Tomography (HRpQCT), that offer more accurate three-dimensional measurements of volumetric BMD (vBMD) and microstructure of distal tibia and radius(4). The aim of this study was to examine the differences in the dietary intake of nutrients that represent organic or inorganic components of the bone, in early postmenopausal women with different spine aBMD and tibia and radius vBMD levels. One hundred and fourteen healthy early postmenopausal women with a lumbar spine or total hip BMD T score &gt; −2.5 (measured by DXA) were recruited as part of a larger interventional study. Dietary intake was recorded using a 297-point self-reported validated food frequency questionnaire(5) for assessing the intake of energy, macro and micronutrients. Physical activity was self-reported using the validated Active Australia Questionnaire. Years since menopause were self-reported. DXA and HRpQCT scans measured L1-L4 spine, proximal femur aBMD, and distal tibia and radius vBMD respectively. Non-parametric statistical tests examined differences in dietary intake and physical activity levels between women at different levels of aBMD and vBMD. Data reported as median and interquartile ranges. There were no significant differences observed in the total sample between tertiles of aBMD and vBMD, regarding nutrient intake. However, for women with less than 3 years since menopause (i.e., the time-period of accelerated bone loss), lower dietary intakes of energy [8,658(3,324) vs 10,068(3,688) kJ/day; p = 0.047], protein [94(29) vs 103(32) g/day; (p = 0.044)], sodium [1,927(992) vs 2,625(2,185) mg/d; (p = 0.044)], potassium [4,064(1,373) vs 5,121(2,377) mg/d; (p = 0.041)], calcium [969(325) vs 1,214(652) mg/d; (p = 0.028)] and zinc [10(3) vs 12(4) mg/d; (p = 0.005)] were observed for women with osteopenia (−1&lt; L1-L4 aBMD T-score &lt;2.5) compared to those with normal L1-L4 aBMD (i.e., T-score &gt; −1). No significant differences were observed for women with more than 3 years since menopause, with the only exception of alcohol intake (p = 0.033), which was found to be lower in women with osteopenia compared to those with normal aBMD. These findings highlight the importance of targeting osteopenic women within the first 3 years following menopause as candidates for tailored dietary intervention programs for preventing osteoporosis.

The effect of forearm rotation on the bone mineral density measurements of the distal radius.

Forearm dual-energy X-ray absorptiometry (DXA) is often performed in clinics where central DXA is unavailable. Accurate bone mineral density (BMD) measurement is crucial for clinical assessment. Forearm rotation can affect BMD measurements, but this effect remains uncertain. Thus, we aimed to conduct a simulation study using CT images to clarify the effect of forearm rotation on BMD measurements. Forearm CT images of 60 women were analyzed. BMD was measured at the total, ultra-distal (UD), mid-distal (MD), and distal 33% radius regions with the radius located at the neutral position using digitally reconstructed radiographs generated from CT images. Then, the rotation was altered from - 30° to 30° (supination set as positive) with a one-degree increment, and the percent BMD changes from the neutral position were quantified for all regions at each angle for each patient. The maximum mean BMD changes were 5.8%, 7.0%, 6.2%, and 7.2% for the total, UD, MD, and distal 33% radius regions, respectively. The analysis of the absolute values of the percent BMD changes from the neutral position showed that BMD changes of all patients remained within 2% when the rotation was between - 5° and 7° for the total region, between - 3° and 2° for the UD region, between - 4° and 3° for the MD region, and between - 3° and 1° for the distal 33% radius region. Subtle rotational changes affected the BMD measurement of each region. The results showed the importance of forearm positioning when measuring the distal radius BMD.

Gonadotropin-Releasing Hormone Agonist Therapy and Longitudinal Bone Mineral Density in Congenital Adrenal Hyperplasia.

Children with congenital adrenal hyperplasia (CAH) are at risk for early puberty. Gonadotropin-releasing hormone analog (GnRHa) is frequently used and can decrease bone mineral density (BMD). Our aim was to investigate the effect of GnRHa therapy on BMD in a longitudinal study of patients with CAH spanning both childhood and adulthood. Sixty-one patients with classic CAH due to 21-hydroxylase deficiency (20 treated with GnRHa) were followed with dual-energy X-ray absorptiometry (DXA) scans at puberty onset, attainment of adult height, and during early adulthood. Whole body, lumbar spine, femoral neck, total hip, and distal radius BMD z-score at adult height. Longitudinal BMD and adult height were also assessed. Twenty patients received GnRHa for an average of 4.5 ± 2 years. There were no differences in BMD between GnRHa-treated and -untreated groups at adult height for all sites. Overall, the follow-up DXA during early adulthood showed decreases in BMD z-scores for whole body (P = .01), lumbar spine (P < .0001), femoral neck (P = .06), total hip (P = .009), and distal radius (P = .05). GnRHa treatment correlated with improved height outcomes compared to predicted height at puberty onset after adjusting for midparental height (P = .02). Patients in both groups achieved similar adult height. In children with CAH, GnRHa does not compromise BMD. However, BMD decreases with time and during the second and third decades of life is a possible effect of chronic supraphysiologic glucocorticoids. Children with CAH who experience early puberty benefit from GnRHa treatment as evidenced by the positive effect on height.

Trabecular bone score and bone mineral density as indices of skeletal fragility in endogenous Cushing's syndrome.

Endogenous Cushing's syndrome (CS) is a known cause of secondary osteoporosis. Vertebral fractures (VFs) in endogenous CS may occur despite normal bone mineral density (BMD). Trabecular bone score (TBS) is a relatively new, non-invasive technique to assess bone microarchitecture. The objective of our study was to analyse the BMD and bone microarchitecture using TBS in endogenous CS and compare it with a group of age and sex-matched healthy controls, and also analyse the factors predicting BMD and TBS. Cross-sectional study of cases and controls. We included 40 female patients with overt endogenous CS, out of which 32 were adrenocorticotropic hormone (ACTH)-dependent CS and 8 were ACTH-independent. We also included 40 healthy, female controls. Both patients and controls were subjected to an assessment of biochemical parameters and BMD and TBS. Patients with endogenous CS had significantly lower BMD at the lumbar spine, femoral neck, and total hip and significantly lower TBS than healthy controls (all p < .001), while no significant difference was noted in the distal radius BMD (p = .055). In endogenous CS, a large proportion of patients, n = 13 (32.5%) had normal BMD for age (BMD Z-score ≥ -2.0) with low TBS (L1 -L4 TBS ≤ 1.34). TBS correlated negatively with HbA1c (p = .006), and positively with serum T4 (p = .027). TBS should be considered an important complementary tool in addition to BMD for the routine assessment of skeletal health in CS.

Paper 02: Distal Radius Allograft for Glenohumeral Instability: A Novel Osteochondral Allograft Reconstruction Option in the Setting of Glenoid Bone Loss

Objectives: Glenoid bone loss in the setting of recurrent shoulder instability remains a challenging surgical problem. The coracoid process and iliac crest currently serve as primary autograft options for glenoid reconstruction. With regards to allograft alternatives, the distal tibia, first described in 2007, has good midterm outcomes when used during an index surgery and in cases of failed prior Latarjet reconstruction. While the distal tibia performs well in reconstructing the glenoid bony defect, it is a nonanatomic reconstruction and does not match the glenoid radius of curvature (ROC) in the anterior to posterior (AP) plane. No prior work has evaluated and described the utilization of the dorsal articular portion of the distal radius as an allograft reconstruction option for recurrent instability with glenoid bony deficiency. The purpose of this study was to evaluate distal radius fresh frozen allograft as a potential match for glenoid reconstruction through assessment of graft ROC and bone mineral density (BMD). Distal tibia allograft was utilized as the primary comparison group with both cadaveric and Computerized Tomography (CT) analysis. Methods: Eighteen fresh-frozen human cadaveric specimens (6 shoulder, 6 wrist, and 6 tibia) were utilized for this study. Specimens without osteoarthritis or prior surgical procedures were included. CT scans were obtained of all specimens to confirm the absence of osteoarthritis, significant joint deformity, or evidence of prior surgical procedure. Specimens were dissected free of all soft tissues except for the glenoid labrum of the shoulder and dorsal wrist ligaments of the distal radius. The ROC for each specimen were independently measured by two fellowship trained shoulder surgeons in both the superior to inferior (SI) and AP planes. Graft length in the SI plane was also assessed. A thirty percent defect was then created in all glenoid specimens and both distal tibia and distal radius grafts were harvested to assess graft fit post-fixation [Figure 1]. CTs were also analyzed to assess bony ROC and BMD for each specimen. Results: On cadaveric analysis, the mean SI graft length of the glenoid was 39.7 mm compared to 36.8 mm for the distal radius and 30.0 mm for the distal tibia [Table 1A]. Average ROC in the SI plane was 29.0 +/- 5.3 for the glenoid, 37.8 +/- 4.9 for the distal radius and 24.0 +/- 3.7 for the distal tibia; in the AP plan average ROC was 39.6 +/- 6.6 for the glenoid, 30.4 +/- 18.6 for the distal radius and 126.3 +/- 9.5 for the distal tibia [Table 1B]. On CT analysis, average ROC in the SI plane was 30.4 +/- 1.5 for the glenoid, 30.3 +/- 5.6 for the distal radius and 24.5 +/- 9.4 for the distal tibia; in the AP plane average ROC was 30.8 +/- 2.0 for the glenoid, 19.1 +/- 2.3 for the distal radius and 46.7 +/- 21.7 for the distal tibia [Table 2A]. Mean BMD was 226.3 +/- 79.0 for the glenoid, 228.5 +/-94.7 for the distal radius, 235.0 +/- 96.2 for the coracoid process, and 235.1 +/- 84.6 for the distal tibia [Table 2B]. Conclusions: Given fresh frozen allograft supply and cost constraints, exploration of additional graft options is necessitated. This study presents distal radius allograft as a novel reconstruction option for patients with anterior glenoid bone loss in the setting of recurrent glenohumeral instability. Compared with the distal tibia allograft, the distal radius had greater graft length in the SI plane providing possible utilization in cases of larger bony defects. The distal radius also has a more acute ROC in the AP plane (closer to that of the glenoid) compared with the distal tibia allograft providing a greater potential buttress to anterior humeral translation. Furthermore, the distal radius also has potential to employ the dorsal radio-carpal ligaments to perform an anterior capsular repair following allograft fixation. Finally, compared to currently utilized grafts (coracoid process and distal tibia), the distal radius BMD was not significantly diminished on CT analysis. This study presents the distal radius as a novel allograft reconstruction option in the setting of glenoid bone loss; further biomechanical and clinical investigation is indicated. [Table: see text][Table: see text]

Bone microarchitecture and bone mineral density in Graves’ disease

ObjectivesGraves' disease (GD) is the most common cause of thyrotoxicosis. There are many studies that have evaluated bone mineral density (BMD) in Graves’ disease. However, the strength of a bone also depends on its microarchitecture which can be assessed by various techniques. Trabecular bone score (TBS) is a new method for assessing bone microarchitecture that is non-invasive and easily performed. MethodsThe present study was a cross-sectional study that involved 50 patients with active GD and 50 healthy controls. Both groups were subjected to an assessment of biochemical parameters followed by measurement of BMD and TBS on the same dual energy X-ray absorptiometry (DXA) machine. ResultsThe mean age of patients with active GD (N = 50) was 31.9 ± 10.9 years while that of controls was 31.2 ± 4.9 years (P = 0.640). The female: male ratio was the same for both groups (F = 31, M = 19). The mean lumbar spine BMD, femoral neck BMD, total hip BMD, and distal radius BMD were significantly reduced in GD when compared to that in controls. The mean absolute lumbar spine TBS in GD was 1.263 ± 0.101 while that in controls was 1.368 ± 0.073 (P < 0.001). On multivariate regression analysis, the factors that predicted TBS were serum thyroxine (T4) and L1-L4 BMD. ConclusionsPatients with Graves’ disease had reduced bone density at all sites and degraded microarchitecture. Long-term studies are required to understand the pattern of recovery of bone microarchitecture after the restoration of euthyroidism.

Effect of low dose denosumab on bone mineral density in postmenopausal women with osteoporosis after a transition from 60 mg dose: a prospective observational study

IntroductionDenosumab is an effective antiresorptive molecule and reduces the risk of fracture in postmenopausal osteoporosis. Cessation of denosumab therapy however is associated with rapid declines in bone mineral density (BMD), rises in bone remodeling, and an increased risk of fracture. We evaluated the effect of low dose denosumab (30 mg every 6 months) on the prevention of bone loss following a switch from standard dose (60 mg of denosumab every 6 months) in a prospective observational study.MethodsWe recruited 114 women 50–90 years of age with postmenopausal osteoporosis at a moderate fracture risk without prior fragility fractures, who had been on denosumab 60 mg every 6 month. These women switched to low dose denosumab 30 mg every 6 months. Mean percentage change in lumbar spine (LS), femoral neck (FN), total hip (TH) and 1/3 distal radius (1/3RAD) BMD at 12 and 24 months were evaluated. Predictors for change in BMD were explored. Subgroup analysis for patients on denosumab 60 mg every 6 months for <3 years and for ≥3 years before switching to low dose denosumab 30 mg was evaluated.ResultsAt 12 months following a switch from 60 mg to 30 mg of denosumab every 6 months we observed an increase in LS BMD mean percentage change (+2.03%, 95% CI 1.18–2.88, p < 0.001). BMD was stable at the hip and radial sites. Age was found to be a predictor of the mean percentage change in LS BMD for the overall sample. At 24 months, there was a further increase in LS BMD mean percentage change (+3.44%, 95% CI 1.74–5.12, p < 0.001), with stable BMD at other skeletal sites. The 12 month mean BMD percentage change at the LS (p = 0.015), FN (p < 0.001), TH (p < 0.001), and 1/3 RAD (p < 0.001) were found to be predictors of the 24 month mean BMD percentage change. No clinical fractures were reported during 24 months of follow up.ConclusionWe observed stable BMD following a switch from denosumab 60 mg every 6 months to 30 mg every 6 months in this prospective observational study conducted in postmenopausal women at a moderate fracture risk

The significance of forearm bone mineral density evaluation in determining surgical indications in primary hyperparathyroidism

PurposeForearm osteoporosis is a well-known complication of primary hyperparathyroidism (PHPT). However, measuring forearm bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) at the distal radius is often neglected in clinical practice despite the fact that osteoporosis at any site is a criterion indicating surgery. We aimed to evaluate the importance and priority of forearm BMD and to determine its association with biochemical parameters. Material and methodsThree hundred fourteen patients (272 females, 42 males) with PHPT who had BMD measurements at 3 sites were recruited for this retrospective study. The effect on surgical indications of osteoporosis only in the forearm was evaluated. Group 1 (n=151) with forearm osteoporosis and group 2 (n=163) without were compared in terms of biochemical and clinical parameters. ResultsIn the overall study population, 165 of the 314 patients had osteoporosis in at least 1 site. Twenty seven percent (n=86/314) had osteoporosis only in the forearm, while the other 2 sites (lumbar spine and femoral neck) were normal or osteopenic. Surgery was indicated based on osteoporosis only in the forearm in 10% of patients (n=30/314). Corrected calcium and parathyroid hormone levels were significantly higher in group 1 than group 2 (p=0.001 and p<0.001, respectively) and were also negatively correlated with distal radius BMD, T-score and Z-score in the whole study group. ConclusionIncluding the distal radius in BMD measurement increased the number of patients diagnosed with osteoporosis and for whom surgery was indicated. Calcium and PTH were also more frequently elevated in patients with forearm osteoporosis. These results show that distal radius BMD is relevant to the management of PHPT.

Evaluation of Increasing Dairy Intake on Bone Density in Postpubertal Youth: A Randomized Controlled Trial Using Motivational Interviewing

Adequate nutrition is important for bone health, especially for bone mineral accretion. The primary objective tested whether increasing dairy intake using the motivational interviewing technique (MInt) improves lumbar spine (LS) bone mineral density (BMD) after 2 y in postpubertal adolescents with habitual dairy intake of <2 dairy servings/d. Participants (aged 14-18.9 y) were randomly allocated to: group 1 (control), group 2 (target of 3 dairy servings/d), or group 3 (target of ≥4 dairy servings/d) for 12 mo, with groups 2 and 3 using MInt, with an additional 12-mo nonintervention follow-up. The primary outcome was LS BMD, and secondary outcomes were: whole body, total hip (TH), and 33% distal radius BMD using DXA, bone geometry using peripheral quantitative computed tomography, and bone biomarkers. Ninety-four adolescents (16.6 ± 1.5 y) were recruited. Seventy-six (80.9%) completed the 12-mo assessments. From baseline to 12 mo, dairy intake in female groups 2 and 3 increased by 107% and 208%, respectively; and by 48% and 153% in males of groups 2 and 3, respectively. In females, group 3 had greater increases in TH BMD (4.3% to 7.5%) compared with control (3.7% to 4.9%, P = 0.04) and group 2 (0.0% to 1.7%, P = 0.04) at 12 and 24 mo. No effects due to dairy intake were observed for DXA outcomes in males for radial and tibial volumetric BMD in both sexes. None of the bone biomarkers were different among the dairy groups in females or males. MInt effectively increased dairy intake with benefits to bone health only in female adolescents with previously low calcium intake who consumed ≥4 dairy servings/d for 12 mo. Larger studies are required to explain the lack of intervention effect in males.

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.

Identifying periods of susceptibility to perfluoroalkyl substances and bone mineral density in early adolescence: the HOME Study

BACKGROUND AND AIM: Perfluoroalkyl substance (PFAS) exposures may affect childhood bone mineral density (BMD), but no studies have assessed periods of heightened susceptibility. We estimated associations of individual PFAS and their mixture during gestation and three times during childhood with BMD in early adolescence. METHODS: We examined 222 mother-child pairs enrolled in a prospective pregnancy and birth cohort in Cincinnati, OH from 2003-2006. We measured concentrations of perfluorooctanoic acid (PFOA), perfluorononanoic acid, perfluorohexanesulfonic acid, and perfluorooctanesulfonic acid in maternal serum collected at 16 weeks gestation and child serum collected at age 3, 8, and 12 years. At age 12 years, we measured areal BMD at six skeletal sites with dual x-ray absorptiometry and calculated height-, age-, sex-, and population ancestry-specific BMD Z-scores. Using linear regression, we estimated covariate-adjusted differences in BMD Z-scores per doubling of PFAS concentrations at each period. Using hierarchical Bayesian kernel machine regression (hBKMR), we estimated period-specific associations and posterior inclusion probabilities (PIPs) to determine periods of heightened susceptibility to PFAS mixtures. RESULTS:Associations were strongest for PFOA and forearm (1/3 distal radius) BMD, with differing periods of susceptibility for males and females. Among males, forearm BMD Z-score differences (95% confidence interval) per doubling of PFOA were -0.26 (-0.50, -0.02), -0.33 (-0.68, 0.02), -0.24 (-0.61, 0.13), and -0.00 (-0.30, 0.29) for gestation and ages 3, 8, and 12, respectively. Among females, the corresponding estimates were -0.12 (-0.38, 0.15), -0.07 (-0.44, 0.30), -0.30 (-0.76, 0.17), and -0.44 (-0.81, -0.07). Patterns were generally similar but weaker for other PFAS and skeletal sites. Period-specific PIPs from hBKMR models were highest for the PFAS mixture at age 8 for males (0.76) and age 12 for females (0.62). CONCLUSIONS:PFOA and PFAS mixtures were associated with lower BMD in early adolescence. Susceptibility to PFAS may occur earlier in life for males compared with females. KEYWORDS: Chemical exposures, Children's environmental health, Mixtures analysis, PFAS, Endocrine disrupting chemicals, Environmental epidemiology

Gestational organophosphate ester exposures and bone mineral density in early adolescence: The HOME Study

BACKGROUND AND AIM: Optimizing bone mineral density (BMD) in adolescence is critical for life-long bone health. Organophosphate esters (OPEs) are synthetic flame retardants and plasticizers that may have osteotoxic effects via endocrine disruption or nuclear receptor agonism. Animal studies suggest that gestation may be a critical period of susceptibility for the impact of OPEs on bone health, but human studies are lacking. We assessed the relation of maternal urinary OPE metabolite concentrations during pregnancy with early adolescent BMD in a prospective birth cohort study. METHODS: We used data from 223 mother-child dyads enrolled in the HOME Study from Cincinnati, OH area, 2003-2006. We measured bis-2-chloroethyl phosphate (BCEP), bis-(1,3-dichloro-2-propyl) phosphate (BDCIPP), di-n-butyl phosphate (DnBP), and diphenyl phosphate (DPHP) in maternal urine collected at 16- and 26-weeks gestation, and calculated the average of creatinine-adjusted concentrations. We performed dual x-ray absorptiometry in children at age 12 years and calculated height-, age-, sex-, and population ancestry-specific Z-scores for whole body (excluding head), total hip, femoral neck, distal radius, and ultradistal radius areal BMD (aBMD) and spine bone mineral apparent density (BMAD). We estimated covariate-adjusted associations per 2-fold increase in maternal urinary OPE concentrations and assessed effect measure modification by child sex. RESULTS:In adjusted analyses, BDCIPP concentrations were positively associated with aBMD and BMAD Z-scores at most skeletal sites. Z-score differences were between 0.11 and 0.15 and greatest for total hip (β = 0.15, 95% CI: 0.02, 0.29). Associations of DPHP with femoral neck and total hip aBMD differed by child sex. Associations among males were null while DPHP concentrations were inversely associated with femoral neck (β = -0.15, 95% CI: -0.29, -0.02) and total hip (β = -0.15, 95% CI: -0.29, 0.00) aBMD Z-scores among females. CONCLUSIONS:Maternal OPE exposures during gestation may affect early adolescent BMD in a metabolite-, sex-, and bone site-specific manner. KEYWORDS: Chemical exposures, Children's environmental health, Endocrine disrupting chemicals

Efficacy and Safety of Postmenopausal Osteoporosis Treatments: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

Although a range of pharmacological interventions is available, it remains uncertain which treatment for osteoporosis is more effective. This network meta-analysis study aimed to compare different drug efficacy and safety in randomized controlled trials (RCTs) for the treatment of postmenopausal osteoporosis. PubMed, EMBASE, MEDLINE, Clinicaltrial.gov, Cochrane library, Google scholar were searched up to 31 October 2020. Randomized placebo-controlled trials that reported measures of bone mineral density (BMD) percentage change and/or numbers of adverse events of postmenopausal osteoporosis patients were included. Network meta-analysis was conducted using frequentist approach. Ninety-four RCTs comprising 15,776 postmenopausal osteoporosis females were included in the network meta-analysis. Compared with placebo, most interventions showed increase in BMD change. According to surfaces under the cumulative ranking curves (SUCRAs), strontium ranelate, fluoride, and hormone replacement therapy were most effective in increasing total hip, lumbar spine, and distal radius BMD, respectively. Parathyroid hormone (PTH) was most effective in preventing new hip fracture. When taking into account all anatomic sites, bisphosphonate (BP), monoclonal antibody (mAb), and fluoride have a balanced efficacy in increasing BMD at all sites. Considering both the effectiveness of increasing BMD and preventing hip fracture, mAb, BP, and PTH are more favorable among all interventions. The treatment effects of different medications on BMD percentage change are anatomic site-dependent. After weighing anti-osteoporosis treatment efficacy against risk of complications, BP and mAb are the more favorable interventions to increase BMD at all sites and reduce the risks of hip fracture and death.

DXA-Based Bone Strain Index: A New Tool to Evaluate Bone Quality in Primary Hyperparathyroidism.

Primary hyperparathyroidism (PHPT) is associated with impaired bone quality and increased fracture risk. Reliable tools for the evaluation of bone quality parameters are not yet clinically available. Bone Strain Index (BSI) is a new metric for bone strength based on Finite Element Analysis from lumbar spine and femoral neck dual-energy x-ray absorptiometry (DXA) images. To assess the lumbar spine (LS), femoral neck (FN), and total hip (TH) BSI in PHPT patients compared with controls and to investigate the association of BSI with vertebral fractures (VFs) in PHPT. This case-control study enrolled 50 PHPT patients and 100 age- and sex-matched control subjects from an outpatient clinic. The main outcome measures were LS-BSI, FN-BSI, and TH-BSI. FN bone mineral density (BMD) and one-third distal radius BMD were lower in the PHPT group than in controls (FN 0.633 ± 0.112 vs 0.666 ± 0.081, P = 0.042; radius 0.566 ± 0.07 vs 0.625 ± 0.06, P < 0.001). PHPT group has significant lower TBS score compared with controls (1.24 ± 0.09 vs 1.30 ± 0.10, P < 0.001). BSI was significantly higher at LS (2.28 ± 0.59 vs 2.02 ± 0.43, P = 0.009), FN (1.72 ± 0.41 vs 1.49 ± 0.35, P = 0.001), and TH (1.51 ± 0.33 vs 1.36 ± 0.25, P = 0.002) in PHPT. LS-BSI showed moderate accuracy for discriminating VFs (AUC 0.667; 95% CI, 0.513-0.820). LS-BSI ≥ 2.2 and was a statistically significant independent predictor of VFs, with an adjusted odds ratio ranging from 5.7 to 15.1. BSI, a DXA-derived bone quality index, is impaired in PHPT and may help to identify PHPT subjects at high risk of fractures.

Bone structure assessed with pQCT in prepubertal males with delayed puberty or congenital hypogonadotropic hypogonadism

Congenital hypogonadotropic hypogonadism (CHH) is associated with impaired bone mineral density in adulthood, whereas the estimates on bone structure in adolescents with CHH has not been previously evaluated. This study describes bone structure in CHH patients and compares it to that in boys with constitutional delay of growth and puberty (CDGP). A cross-sectional study. Peripheral quantitative computed tomography (pQCT) of non-dominant arm and left leg were performed. Volumetric bone mineral density (BMD), bone mineral content, and area in trabecular and cortical bone compartments were evaluated, and bone age-adjusted Z-scores for the bone parameters were determined. The participants with CHH had more advanced bone age and were older, taller and heavier than the CDGP boys, yet they had lower trabecular BMD in distal radius (147.7mg/mm3 [95% CI, 128-168mg/mm3 ] vs. 181.2mg/mm3 [172-192mg/mm3 ], p=.002) and distal tibia (167.6mg/mm3 [145-190mg/mm3 ] vs. 207.2mg/mm3 [187-227mg/mm3 ], p=.012), respectively. CHH males had lower cortical thickness at diaphyseal tibia than the participants with CDGP (p=.001). These between-group differences remained significant in corresponding Z-scores adjusted for bone age and height (p=.001). In CDGP group, serum testosterone correlated positively with trabecular BMD (r=0.51, p=.013) at distal radius, and estradiol levels correlated positively with trabecular BMD at the distal site of tibia (r=0.58, p=.004). Five treatment-naïve male patients with CHH exhibited poorer trabecular BMD than untreated males with CDGP. We speculate that timely low-dose sex steroid replacement in CHH males may benefit skeletal health in adulthood.

Association and predictive value of geriatric nutritional risk index, body composition, or bone mineral density in haemodialysis patients.

Assess the association and predictive value of geriatric nutritional risk index (GNRI), body composition, and bone mineral density (BMD) in haemodialysis (HD) patients. Laboratory data, body composition parameters measured via body composition monitor, and radius, lumbar spine, femoral neck BMD measured using dual energy X-ray absorptiometry were assessed in all subjects on HD or online haemodiafiltration (HDF) at baseline. Regression analysis for GNRI, Cox proportional hazard analyses and comparison of multiple receiver operating characteristic (ROC) curves were performed. Among all 264 patients, age was 65 ± 12 years and dialysis vintage was 79 (39-144) months. GNRI tertile (T)1, T2, and T3 were 88 (85-91), 94 (93-95), and 98 (97-101), respectively. Patients in GNRI T1 had lower fat tissue index (FTI), lean tissue index, and femoral neck, lumbar spine, and distal mid-third radius BMD, but higher overhydration/extracellular fluid than patients in GNRI T2 or T3 (P < .05). GNRI was significantly associated with FTI, lean tissue index, and femoral neck, lumbar spine, and distal mid-third radius BMD (P < .01). GNRI was a significant predictor of 2-year all-cause mortality (HR 0.92, P < .05). Area under the ROC curve for all-cause mortality using traditional risk factors (age, sex, diabetes mellitus, cardiovascular disease, use of vasopressors for dialysis-related hypotension, and C-reactive protein) was 0.67 and changed by adding GNRI (0.78, P < .05), FTI (0.75), or femoral neck BMD (0.66), respectively. Associations between GNRI, body composition, and BMD were confirmed in HD patients. Combining GNRI with traditional risk factors improved mortality prediction in HD patients.

Is There Difference of BMD between Non-Obese and Obese Children? - A Cross-Sectional Study in 194 Thai Children

Objective: To find the correlation between the presence of childhood obesity and bone mineral density (BMD). Materials and Methods: A cross-sectional study was conducted among children aged between 5 and 12 years old. After excluding children who had history of endocrinopathy, epilepsy, or cerebral palsy, all participants were divided into “obese group” (body mass index [BMI] at or above the 95 percentile of those with the same age and gender) and “control group” (BMI below the 95 percentile). Skeletal age, BMD, serum bone markers (osteocalcin and beta-crosslaps), and physical exercise were collected. Multivariate regression analysis was used for statistical analysis. Results: Ninety-six obese children and 98 controls were included in the present study. The average BMI was 28.5 kg/m² in obese group, and 16.6±1.9 kg/m² in controls (p&lt;0.001). BMDs of the spine and hip area were significantly higher in obese group compared to controls (p=0.002 and &lt;0.001, respectively). However, there was no significant difference of skeletal age or serum bone markers level between both groups (p&gt;0.05 all). Exercise was shown to significantly correlated with hip and distal radius BMD (p&lt;0.001 and 0.003, respectively). Conclusion: Obese children had significantly higher spine and hip BMD than non-obese children. Nevertheless, there were no differences between groups regarding skeletal age and bone markers. BMI and exercise activity might play an important role in higher BMD in children. Keywords: Bone mineral density, Children obesity

Osteoporosis in Parkinson's Disease: Relevance of Distal Radius Dual-Energy X-Ray Absorptiometry (DXA) and Sarcopenia

Osteoporotic fractures are common in Parkinson's disease (PD). Standard dual-energy X-ray absorptiometry (DXA) measuring bone mineral density (BMD) at the femoral neck and lumbar spine (central sites) has suboptimal sensitivity in predicting fracture risk in the general population. An association between sarcopenia and osteoporosis in PD has not been studied. We compared BMD and osteoporosis prevalence in PD patients vs controls; determined the osteoporosis detection rates using central alone vs central plus distal radius DXA; and analyzed factors (in particular, sarcopenia) associated with osteoporosis. One hundred and fifty-six subjects (102 patients with PD, 54 spousal/sibling controls) underwent femoral neck-lumbar spine-distal radius DXA. Seventy-three patients and 46 controls were assessed for sarcopenia using whole-body DXA and handgrip strength. Patients underwent clinical and serum biochemical evaluations. PD patients had significantly lower body mass index compared to controls. After adjustment for possible confounders, distal radius BMD and T-scores were significantly lower in PD patients compared to controls, but not at the femoral neck/lumbar spine. With distal radius DXA, an additional 11.0% of patients were diagnosed with osteoporosis (32.0% to 43.0%), vs 3.7% in controls (33.3% to 37.0%) additionally diagnosed; this increase was largely driven by the markedly higher detection rate in female PD patients. Female gender (adjusted odds ratio [ORadjusted] = 11.3, 95% confidence interval [CI]: 2.6–48.6) and sarcopenia (ORadjusted = 8.4, 95% CI: 1.1–64.9) were independent predictors for osteoporosis in PD. Distal radius DXA increased osteoporosis detection, especially in female PD patients, suggesting that diagnostic protocols for osteoporosis in PD could be optimized. A close association between osteoporosis and sarcopenia was documented for the first time in PD, which has important implications for clinical management and future research.