Bone Geometry,Volumetric Density,Microarchitecture, and Estimated Bone Strength Assessed by HR‐pQCT in Klinefelter Syndrome

Although the expected skeletal manifestations of testosterone deficiency in Klinefelter's syndrome (KS) are osteopenia and osteoporosis, the structural basis for this is unclear. The aim of this study was to assess bone geometry, volumetric bone mineral density (vBMD), microarchitecture, and estimated bone strength using high‐resolution peripheral quantitative computed tomography (HR‐pQCT) in patients with KS. Thirty‐one patients with KS confirmed by lymphocyte chromosome karyotyping aged 35.8 ± 8.2 years were recruited consecutively from a KS outpatient clinic and matched with respect to age and height with 31 healthy subjects aged 35.9 ± 8.2 years. Dual‐energy X‐ray absorptiometry (DXA) and HR‐pQCT were performed in all participants, and blood samples were analyzed for hormonal status and bone biomarkers in KS patients. Twenty‐one KS patients were on long‐term testosterone‐replacement therapy. In weight‐adjusted models, HR‐pQCT revealed a significantly lower cortical area (p < 0.01), total and trabecular vBMD (p = 0.02 and p = 0.04), trabecular bone volume fraction (p = 0.04), trabecular number (p = 0.05), and estimates of bone strength, whereas trabecular spacing was higher (p = 0.03) at the tibia in KS patients. In addition, cortical thickness was significantly reduced, both at the radius and tibia (both p < 0.01). There were no significant differences in indices of bone structure, estimated bone strength, or bone biomarkers in KS patients with and without testosterone therapy. This study showed that KS patients had lower total vBMD and a compromised trabecular compartment with a reduced trabecular density and bone volume fraction at the tibia. The compromised trabecular network integrity attributable to a lower trabecular number with relative preservation of trabecular thickness is similar to the picture found in women with aging. KS patients also displayed a reduced cortical area and thickness at the tibia, which in combination with the trabecular deficits, compromised estimated bone strength at this site. © 2014 American Society for Bone and Mineral Research.     

Associations of 25‐Hydroxyvitamin D and 1,25‐Dihydroxyvitamin D With Bone Mineral Density,Bone Mineral Density Change,and Incident Nonvertebral Fracture

Relationships between 1,25‐dihydroxyvitamin D (1,25(OH)₂D) and skeletal outcomes are uncertain. We examined the associations of 1,25(OH)₂D with bone mineral density (BMD), BMD change, and incident non‐vertebral fractures in a cohort of older men and compared them with those of 25‐hydroxyvitamin D (25OHD). The study population included 1000 men (aged 74.6 ± 6.2 years) in the Osteoporotic Fractures in Men (MrOS) study, of which 537 men had longitudinal dual‐energy X‐ray absorptiometry (DXA) data (4.5 years of follow‐up). A case‐cohort design and Cox proportional hazards models were used to test the association between vitamin D metabolite levels and incident nonvertebral and hip fractures. Linear regression models were used to estimate the association between vitamin D measures and baseline BMD and BMD change. Interactions between 25OHD and 1,25(OH)₂D were tested for each outcome. Over an average follow‐up of 5.1 years, 432 men experienced incident nonvertebral fractures, including 81 hip fractures. Higher 25OHD was associated with higher baseline BMD, slower BMD loss, and lower hip fracture risk. Conversely, men with higher 1,25(OH)₂D had lower baseline BMD. 1,25(OH)₂D was not associated with BMD loss or nonvertebral fracture. Compared with higher levels of calcitriol, the risk of hip fracture was higher in men with the lowest 1,25(OH)₂D levels (8.70 to 51.60 pg/mL) after adjustment for baseline hip BMD (hazard ratio [HR] = 1.99, 95% confidence interval [CI] 1.19–3.33). Adjustment of 1,25(OH)₂D data for 25OHD (and vice versa) had little effect on the associations observed but did attenuate the hip fracture association of both vitamin D metabolites. In older men, higher 1,25(OH)₂D was associated with lower baseline BMD but was not related to the rate of bone loss or nonvertebral fracture risk. However, with BMD adjustment, a protective association for hip fracture was found with higher 1,25(OH)₂D. The associations of 25OHD with skeletal outcomes were generally stronger than those for 1,25(OH)₂D. These results do not support the hypothesis that measures of 1,25(OH)₂D improve the ability to predict adverse skeletal outcomes when 25OHD measures are available. © 2015 American Society for Bone and Mineral Research.     

High‐Density Association Study of 383 Candidate Genes for Volumetric BMD at the Femoral Neck and Lumbar Spine Among Older Men

Genetics is a well‐established but poorly understood determinant of BMD. Whereas some genetic variants may influence BMD throughout the body, others may be skeletal site specific. We initially screened for associations between 4608 tagging and potentially functional single nucleotide polymorphisms (SNPs) in 383 candidate genes and femoral neck and lumbar spine volumetric BMD (vBMD) measured from QCT scans among 862 community‐dwelling white men ≥65 yr of age in the Osteoporotic Fractures in Men Study (MrOS). The most promising SNP associations (p < 0.01) were validated by genotyping an additional 1156 white men from MrOS. This analysis identified 8 SNPs in 6 genes (APC, DMP1, FGFR2, FLT1, HOXA, and PTN) that were associated with femoral neck vBMD and 13 SNPs in 7 genes (APC, BMPR1B, FOXC2, HOXA, IGFBP2, NFATC1, and SOST) that were associated with lumbar spine vBMD in both genotyping samples (p < 0.05). Although most associations were specific to one skeletal site, SNPs in the APC and HOXA gene regions were associated with both femoral neck and lumbar spine BMD. This analysis identifies several novel and robust genetic associations for volumetric BMD, and these findings in combination with other data suggest the presence of genetic loci for volumetric BMD that are at least to some extent skeletal‐site specific.     

Impact of calcium and vitamin D insufficiencies on serum parathyroid hormone and bone mineral density: Analysis of the fourth and fifth Korea National Health and Nutrition Examination Survey (KNHANES IV‐3, 2009 and KNHANES V‐1, 2010)

The relative contributions of calcium and vitamin D to calcium metabolism and bone mineral density (BMD) have been examined previously, but not in a population with very low calcium intake. To determine the relative importance of dietary calcium intake and serum 25‐hydroxyvitamin D [25(OH)D] concentration to calcium metabolism and bone mass in a population with low calcium intake, a total of 4662 adults (2567 men and 2095 women) ≥50 years of age from the 2009–2010 Korea National Health and Nutrition Examination Survey (KNHANES) were divided into groups according to dietary calcium intakes (quintiles means: 154, 278, 400, 557, and 951 mg/d) and serum 25(OH)D concentrations (<50, 50–75, and >75 nmol/L). Serum intact parathyroid hormone (PTH) and femoral neck and lumbar spine BMD were evaluated according to dietary calcium intake and serum 25(OH)D. Mean calcium intake was 485 mg/d; mean serum 25(OH)D concentration was 48.1 nmol/L; PTH was 68.4 pg/mL; femoral neck BMD was 0.692 g/cm²; and lumbar spine BMD was 0.881 g/cm². Lower dietary calcium intakes were significantly associated with higher serum PTH concentrations and lower femoral neck BMD, not only at lower (<50 nmol/L) but also at higher (>75 nmol/L) serum 25(OH)D concentrations. Serum PTH was highest and femoral neck BMD was lowest in the group, with a serum 25(OH)D less than 50 nmol/L. In this low‐intake population, calcium intake is a significant determinant of serum PTH and BMD at higher as well as lower 25(OH)D levels. This finding indicates that low calcium intake cannot be compensated for with higher 25(OH)D levels alone. As expected, serum 25(OH)D levels were inversely associated with serum PTH and BMD. A calcium intake of at least 668 mg/d and a serum 25(OH)D level of at least 50 nmol/L may be needed to maintain bone mass in this calcium deficient population. © 2013 American Society for Bone and Mineral Research.     

Bone Geometry,Volumetric Density,Microarchitecture, and Estimated Bone Strength Assessed by HR‐pQCT in Adult Patients With Hypophosphatemic Rickets

Hypophosphatemic rickets (HR) is characterized by a generalized mineralization defect. Although densitometric studies have found the patients to have an elevated bone mineral density (BMD), data on bone geometry and microstructure are scarce. The aim of this cross‐sectional in vivo study was to assess bone geometry, volumetric BMD (vBMD), microarchitecture, and estimated bone strength in adult patients with HR using high‐resolution peripheral quantitative computed tomography (HR‐pQCT). Twenty‐nine patients (aged 19 to 79 years; 21 female, 8 male patients), 26 of whom had genetically proven X‐linked HR, were matched with respect to age and sex with 29 healthy subjects. Eleven patients were currently receiving therapy with calcitriol and phosphate for a median duration of 29.1 years (12.0 to 43.0 years). Because of the disproportionate short stature in HR, the region of interest in HR‐pQCT images at the distal radius and tibia were placed in a constant proportion to the entire length of the bone in both patients and healthy volunteers. In age‐ and weight‐adjusted models, HR patients had significantly higher total bone cross‐sectional areas (radius 36%, tibia 20%; both p < 0.001) with significantly higher trabecular bone areas (radius 49%, tibia 14%; both p < 0.001) compared with controls. In addition, HR patients had lower total vBMD (radius ?20%, tibia ?14%; both p < 0.01), cortical vBMD (radius ?5%, p < 0.001), trabecular number (radius ?13%, tibia ?14%; both p < 0.01), and cortical thickness (radius ?19%; p < 0.01) compared with controls, whereas trabecular spacing (radius 18%, tibia 23%; p < 0.01) and trabecular network inhomogeneity (radius 29%, tibia 40%; both p < 0.01) were higher. Estimated bone strength was similar between the groups. In conclusion, in patients with HR, the negative impact of lower vBMD and trabecular number on bone strength seems to be compensated by an increase in bone diameter, resulting in HR patients having normal estimates of bone strength. © 2014 American Society for Bone and Mineral Research.     

Longitudinal Change in Bone Density,Geometry, and Estimated Bone Strength in Older Men and Women From The Gambia: Findings From the Gambian Bone and Muscle Aging Study (GamBAS)

Musculoskeletal aging in the most resource-limited countries has not been quantified, and longitudinal data are urgently needed to inform policy. The aim of this prospective study was to describe musculoskeletal aging in Gambian adults. A total of 488 participants were recruited stratified by sex and 5-year age band (aged 40 years and older); 386 attended follow-up 1.7 years later. Outcomes were dual-energy X-ray absorptiometry (DXA) (n = 383) total hip areal bone mineral density (aBMD), bone mineral content (BMC), bone area (BA); peripheral quantitative computed tomography (pQCT) diaphyseal and epiphyseal radius and tibia (n = 313) total volumetric BMD (vBMD), trabecular vBMD, estimated bone strength indices (BSIc), cross-sectional area (CSA), BMC, and cortical vBMD. Mean annualized percentage change in bone outcomes was assessed in 10-year age bands and linear trends for age assessed. Bone turnover markers, parathyroid hormone (PTH), and 25-hydroxyvitamin D (25(OH)D) were explored as predictors of change in bone. Bone loss was observed at all sites, with an annual loss of total hip aBMD of 1.2% in women after age 50 years and in men at age 70 years plus. Greater loss in vBMD and BSIc was found at the radius in both men and women; strength was reduced by 4% per year in women and 3% per year in men (p trend 0.02, 0.03, respectively). At cortical sites, reductions in BMC, CSA, and vBMD were observed, being greatest in BMC in women, between 1.4% and 2.0% per annum. Higher CTX and PINP predicted greater loss of trabecular vBMD in women and BMC in men at the radius, and higher 25(OH)D with less loss of tibial trabecular vBMD and CSA in women. The magnitude of bone loss was like those reported in countries where fragility fracture rates are much higher. Given the predicted rise in fracture rates in resource-poor countries such as The Gambia, these data provide important insights into musculoskeletal health in this population. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).     

Meal conditions affect the absorption of supplemental vitamin D3 but not the plasma 25‐hydroxyvitamin D response to supplementation

It is sometimes assumed that dietary fat is required for vitamin D absorption, although the impact of different amounts of dietary fat on vitamin D absorption is not established. This study was conducted to determine whether the presence of a meal and the fat content of the meal influences vitamin D absorption or the 25‐hydroxyvitamin D [25(OH)D] response to supplemental vitamin D₃. Based on earlier studies in rats we postulated that absorption would be greatest in the low‐fat meal group. Sixty‐two healthy older men and women were randomly assigned to one of three meal groups: no meal, high‐fat meal, or low‐fat meal; each was given a monthly 50,000 IU vitamin D₃ supplement with the test breakfast meal (or after a fast for the no‐meal group) and followed for 90 days. Plasma vitamin D₃ was measured by liquid chromatography–mass spectroscopy (LC/MS) before and 12 hours after the first dose; plasma 25(OH)D was measured by radioimmunoassay at baseline and after 30 and 90 days. The mean 12‐hour increments in vitamin D₃, after adjusting for age and sex, were 200.9 nmol/L in the no‐meal group, 207.4 nmol/L in the high‐fat meal group, and 241.1 nmol/L in the low‐fat meal group (p = 0.038), with the increase in the low‐fat group being significantly greater than the increases in the other two groups. However, increments in 25(OH)D levels at 30 and 90 days did not differ significantly in the three groups. We conclude that absorption was increased when a 50,000 IU dose of vitamin D was taken with a low‐fat meal, compared with a high‐fat meal and no meal, but that the greater absorption did not result in higher plasma 25(OH)D levels in the low‐fat meal group.     

U‐Shaped Association Between Serum 25‐Hydroxyvitamin D and Fracture Risk in Older Men: Results From the Prospective Population‐Based CHAMP Study

The aim of this population‐based, prospective, observational study was to examine the relationship between serum levels of 25‐hydroxyvitamin D (25OHD) and fracture risk in a cohort of 1662 community‐dwelling men aged 70 to 97 years followed for a mean of 4.3 years. Data about mobility, muscle strength, balance, medication use, cognition, medical history, lifestyle factors, renal function, and serum 25OHD were collected at baseline. Data on radiologically verified fractures were collected every 4 months. The relationship between fractures and serum 25OHD levels was analyzed using Cox's proportional hazard regression. We accounted for bone mineral density, falls, physical activity, sun exposure, and season of blood draw, in addition to anthropometric and lifestyle factors, medical history, muscle strength, balance, and medication and supplement use. There were 123 first‐incident fragility fractures. The relationship between baseline 25OHD and fracture risk was U‐shaped, with increased fracture risk in men with either low or high serum 25OHD levels. In multivariate analysis, the risk of fracture was greatest in men with 25OHD levels in the lowest quintile (25OHD ≤36 nmol/L; hazard ratio [HR] = 3.5; 95% confidence interval [CI] 1.7–7.0) and in men in the highest quintile (25OHD >72 nmol/L; HR = 2.7; 95% CI 1.4–5.4) compared with men in the 4th quintile (25OHD ≥60 to ≤72 nmol/L). These associations were not explained by lower BMD, increased physical activity, fall risk, or other lifestyle or anthropomorphic factors. In community‐dwelling older men, there appears to be a healthy target range for serum 25OHD concentrations. Thus, serum 25OHD levels too high and too low may be harmful in regard to fracture risk. © 2014 American Society for Bone and Mineral Research.     

Dietary Calcium and Serum 25‐Hydroxyvitamin D Status in Relation to BMD Among U.S. Adults

A higher calcium intake is still the primary recommendation for the prevention of osteoporosis, whereas vitamin D deficiency is often not addressed. To study the relative importance of dietary calcium intake and serum 25‐hydroxyvitamin D [25(OH)D] status in regard to hip BMD, 4958 community‐dwelling women and 5003 men ≥20 yr of age from the U.S. NHANES III population‐based survey were studied. Calcium supplement users and individuals with a prior radius or hip fracture were excluded. We calculated standardized means for BMD by quartiles of sex‐specific calcium intake for three 25(OH)D categories (<50, 50–74, and 75+ nM) among men and women, separately controlling for other important predictors of BMD. A higher calcium intake was significantly associated with higher BMD (p value for trend: p = 0.005) only for women with 25(OH)D status <50 nM, whereas calcium intake beyond the upper end of the lowest quartile (>566 mg/d) was not significantly associated with BMD at 25(OH)D concentrations >50 nM. Among men, there was no significant association between a higher calcium intake beyond the upper end of the lowest quartile (626 mg/d) and BMD within all 25(OH)D categories. Among both sexes, BMD increased stepwise and significantly with higher 25(OH)D concentrations (<50, 50–74, 75+ nM; p value for trend: women < 0.0001; men = 0.0001). Among men and women, 25(OH)D status seems to be the dominant predictor of BMD relative to calcium intake. Only women with 25(OH)D concentrations <50 nM seem to benefit from a higher calcium intake.     

岳阳地区50岁以上人群25经维生素D水平及其与骨密度的关系

目的 通过测定269名岳阳地区50岁以上人群血清25经维生素D(25(OH)D)和骨密度(BMD)水平,分析岳阳地区50岁以上人群的维生素D ( VitD)状况,并探讨其与BMD的关系。方法 采集受试者的血清后,用电化学发光法测定血清25(OH)D水平,并同时应用双能X线吸收仪测定腰椎及髓部BMD。结果 所有受试者中,VitD严重缺乏者占24. 2 %,缺乏者占45. 0%,不足者占24. 5 %,充足者占6. 3。男、女性受试者的25(OH)D水平、腰椎及髓部的BMD间有统计学差异(P<0.001),男性高于女性。男性各年龄段间25(OH)D水平及各部位BMD无统计学差异(P=0. 101 ,P = 0. 261 ,0. 055 ,0. 170 ,0. 108 ,0. 051 ) ;女性各年龄段之间25(OH)D水平及腰椎BMD无统计学差异(P = 0. 364 , 0. 063 ) ;髓部BMD有统计学差异(P < 0. 001 ),随着年龄的增长而逐步减低。男性受试者中,不同25(OH)D水平组间股骨颈、转子间区及整髓BMD无统计学差异(P = 0. 076 , 0. 425 , 0. 122 );腰椎、大转子区BMD水平间有统计学差异(P=0. 027 , 0. 017 ) , VitD充足组腰椎BMD高于其他各组(P = 0. 005 , 0. 025 , 0. 009 );不足组、严重缺乏组大转子区BMD高于缺乏组(P = 0. 021, 0. 005 )。女性受试者中,不同25(OH)D水平组各部位BMD均无统计学差异(P = 0. 616 , 0. 739 , 0. 559 ; 0. 608 , 0. 641)。结论 在湖南岳阳地区50岁以上人群存在严重的维生素D缺乏及不足;对于维生素D状况与骨密度之间可能无直接关联,需加大样本量进一步观察。     

Adverse interaction of low‐calcium diet and low 25(OH)D levels on lumbar spine mineralization in late‐pubertal girls

No consensus has been reached on the serum 25‐hydroxyvitamin D [25(OH)D] levels required to ensure optimal bone health around menarche. We searched for a possible interaction of 25(OH)D levels and calcium intake on lumbar spine mineralization and on biologic features of bone metabolism in healthy late‐pubertal girls. Lumbar spine parameters (ie, area, mineral content, and density) and calcium intake were evaluated in 211 healthy white adolescent girls at pubertal stages IV–V (11 to 16.9 years), together with biologic markers of calcium and bone metabolism and with International External Quality Assessment Scheme for Vitamin D Metabolite (DEQAS)–validated serum 25(OH)D levels. A high prevalence of 25(OH)D levels ≤ 30 nmol/L (41%), ≤40 nmol/L (61%), and ≤50 nmol/L (70%) was found during winter–spring. Parathyroid hormone (PTH) levels were inversely associated with 25(OH)D levels (p = .0021). In contrast, lumbar spine mineral content and density were not associated with 25(OH)D, excepted when calcium intake was below 600 mg/day (p = .0081). Girls with such low calcium intake and 25(OH)D levels of 40 nmol/L or less (9% of the cohort) had a 0.4 to 0.7 SD lower mean areal bone mineral density Z‐score than girls with higher calcium intake and/or higher 25(OH)D status. The adverse association between lumbar spine mineralization and combined calcium deficiency–low 25(OH)D levels remained significant in the 91 girls who could be followed over 4 years after their initial evaluation. We conclude that low 25(OH)D levels (≤40 nmol/L) are observed frequently during winter–spring in late‐pubertal European girls, which may exacerbate the negative impact of calcium deficiency on lumbar spine mineralization. © 2010 American Society for Bone and Mineral Research.     

23(S)25(R)-1,25-Dihydroxyvitamin D3-lactone, a naturally occurring metabolite of 1,25-dihydroxyvitamin D3, inhibits osteoclast-like cell formation in human bone marrow cultures

We have used a human bone marrow culture system that forms multinucleated cells (MNCs), 50% of which express the osteoclast phenotype, to examine the 23(S)25(R)-1,25-dihydroxyvitamin D₃-26,23-lactone (1,25-D₃-lactone) on osteoclast-like cell formation. The 1,25-D₃-lactone is a vitamin D₃ metabolite that has recently been detected in human serum under physiological conditions at concentrations of approximately 131 pg/ml (3 × 10⁻¹⁰ M) and can inhibit bone resorption induced by 1,25-dihydroxyvitamin D₃ (1,25-D₃) in vivo and in vitro. We examined the effects of the 1,25-D₃-lactone on the formation of MNC that cross-reacted with 23C6 monoclonal antibody (23C6-positive MNC), which preferentially binds to osteoclasts. All metabolites of 1,25-D₃ except the 1,25-D3-lactone increased both total and 23C6-positive MNC formation in a dose-dependent manner. In contrast, the 1,25-D₃-lactone inhibited both total and 23C6-positive MNC formation, whether the cultures were treated with 1,25-D₃, parathyroid hormone, or interleukin-1β, all potent stimulators of MNC formation. This inhibitory action of 1,25-D₃-lactone on MNC formation was very similar to the inhibitory effects of calcitonin. These data suggest that (1) 1,25-D₃-lactone is a potent natural inhibitor of formation of cells with the osteoclast phenotype at physiological concentrations and (2) the inhibition of these cells by 1,25-D₃-lactone may not result solely from its competitive binding to the 1,25-D₃ receptor. Received: April 24, 1997 / Accepted: May 30, 1997     

Sex Differences and Growth‐Related Adaptations in Bone Microarchitecture,Geometry, Density,and Strength From Childhood to Early Adulthood: A Mixed Longitudinal HR‐pQCT Study

Sex differences in bone strength and fracture risk are well documented. However, we know little about bone strength accrual during growth and adaptations in bone microstructure, density, and geometry that accompany gains in bone strength. Thus, our objectives were to (1) describe growth related adaptations in bone microarchitecture, geometry, density, and strength at the distal tibia and radius in boys and girls; and (2) compare differences in adaptations in bone microarchitecture, geometry, density, and strength between boys and girls. We used HR‐pQCT at the distal tibia (8% site) and radius (7% site) in 184 boys and 209 girls (9 to 20 years old at baseline). We aligned boys and girls on a common maturational landmark (age at peak height velocity [APHV]) and fit a mixed effects model to these longitudinal data. Importantly, boys showed 28% to 63% greater estimated bone strength across 12 years of longitudinal growth. Boys showed 28% to 80% more porous cortices compared with girls at both sites across all biological ages, except at the radius at 9 years post‐APHV. However, cortical density was similar between boys and girls at all ages at both sites, except at 9 years post‐APHV at the tibia when girls’ values were 2% greater than boys’. Boys showed 13% to 48% greater cortical and total bone area across growth. Load‐to‐strength ratio was 26% to 27% lower in boys at all ages, indicating lower risk of distal forearm fracture compared with girls. Contrary to previous HR‐pQCT studies that did not align boys and girls at the same biological age, we did not observe sex differences in Ct.BMD. Boys’ superior bone size and strength compared with girls may confer them a protective advantage. However, boys’ consistently more porous cortices may contribute to their higher fracture incidence during adolescence. Large prospective studies using HR‐pQCT that target boys and girls who have sustained a fracture are needed to verify this. © 2016 American Society for Bone and Mineral Research.     

Importance of Albumin, 25(OH)-Vitamin D and IGFBP-3 as Risk Factors in Elderly Women and Men with Hip Fracture

The relative importance of vitamin D deficiency, secondary hyperparathyroidism, nutritional deficiency and low bone mineral density (BMD) as risk factors for hip fracture is not definitely established. In the framework of a case-control study of risk factors for hip fractured, biochemical markers of bone metabolism and nutrition and femoral BMD data were compared in 136 female and 43 male hip fracture patients, 126 female and 44 male age-matched hospitalized controls, and 47 healthy elderly women (8 men). Patients with hip fracture had lower albumin (−10%9 and 25(OH)-vitamin D (25(OH)D; −19%) compared with hospitalized controls, and lower albumin (−28%) and 25(OH)D levels (−52%) compared with the elderly controls. Serum values of IGFBP-3 were also significantly lower (−33%) in hip fracture patients than in community controls. BMD of femoral neck was lower (p < 0.001) in patients than in hospitalized and community controls. In hip fracture patients, parathyroid hormone (PTH) correlated weakly with BMD (neck: r = −0.19, trochanter: r = −0.17; both p < 0.05). When all women were pooled (n = 233), albumin correlated significantly (age-adjusted) with BMD at all sites (neck: r = 0.27, trochanter: r = 0.25; all p < 0.001). Albumin, but not 25(OH)D, also correlated with skinfold thickness (r = 0.19, p < 0.0025) and with body mass index (BMI) (r = 0.14, p < 0.05). Male patients with hip fracture had lower BMD and albumin (both p < 0.001), 25(OH)D (p = 0.02) and IGFBP-3 levels (p <: 0.005) compared with the controls. When male patients and controls were pooled together, albumin, skinfold thickness and BMI were significantly correlated with each other, but not with BMD. IGFBP-3 was highly correlated with albumin (p < 0.0001), 25(OH)D (p < 0.005) and, less significantly, with PTH (p < 0.05), but not with BMI or skinfold thickness. IGFBP-3 was significantly correlated with BMD at all sites (neck: r = 0.27, p < 0.05); trochanter: r = 0.40, p < 0.0005). In conclusion, low albumin and low BMD were both important risk factors for hip fracture. Low serum albumin was the strongest independent variable correlated with hip fractures. In men, IGFBP-3 was correlated with BMD. The femoral BMD depended only weakly on PTH and 25(OH)D, but was correlated at all sites with albumin, a non-specific parameter of nutrition and general health.     

Bone Geometry,Volumetric Density,Microarchitecture, and Estimated Bone Strength Assessed by HR‐pQCT in Adult Patients With Type 1 Diabetes Mellitus

The primary goal of this cross‐sectional in vivo study was to assess peripheral bone microarchitecture, bone strength, and bone remodeling in adult type 1 diabetes (T1D) patients with and without diabetic microvascular disease (MVD+ and MVD–, respectively) and to compare them with age‐, gender‐, and height‐matched healthy control subjects (CoMVD+ and CoMVD–, respectively). The secondary goal was to assess differences in MVD– and MVD+ patients. Fifty‐five patients with T1DM (MVD+ group: n = 29) were recruited from the Funen Diabetes Database. Dual‐energy X‐ray absorptiometry (DXA), high‐resolution peripheral quantitative computed tomography (HR‐pQCT) of the ultradistal radius and tibia, and biochemical markers of bone turnover were performed in all participants. There were no significant differences in HR‐pQCT parameters between MVD– and CoMVD– subjects. In contrast, MVD+ patients had larger total and trabecular bone areas (p = 0.04 and p = 0.02, respectively), lower total, trabecular, and cortical volumetric bone mineral density (vBMD) (p < 0.01, p < 0.04, and p < 0.02, respectively), and thinner cortex (p = 0.03) at the radius, and lower total and trabecular vBMD (p = 0.01 and p = 0.02, respectively) at the tibia in comparison to CoMVD+. MVD+ patients also exhibited lower total and trabecular vBMD (radius p = 0.01, tibia p < 0.01), trabecular thickness (radius p = 0.01), estimated bone strength, and greater trabecular separation (radius p = 0.01, tibia p < 0.01) and network inhomogeneity (radius p = 0.01, tibia p < 0.01) in comparison to MVD– patients. These differences remained significant after adjustment for age, body mass index, gender, disease duration, and glycemic control (average glycated hemoglobin over the previous 3 years). Although biochemical markers of bone turnover were significantly lower in MVD+ and MVD– groups in comparison to controls, they were similar between the MVD+ and MVD– groups. The results of our study suggest that the presence of MVD was associated with deficits in cortical and trabecular bone vBMD and microarchitecture that could partly explain the excess skeletal fragility observed in these patients. © 2015 American Society for Bone and Mineral Research.     

Leptin stimulates fibroblast growth factor 23 expression in bone and suppresses renal 1α,25‐dihydroxyvitamin D3 synthesis in leptin‐deficient ob/ob Mice

Leptin is the LEP (ob) gene product secreted by adipocytes. We previously reported that leptin decreases renal expression of the 25‐hydroxyvitamin D₃ 1α‐hydroxylase (CYP27B1) gene through the leptin receptor (ObRb) by indirectly acting on the proximal tubules. This study focused on bone‐derived fibroblast growth factor 23 (FGF‐23) as a mediator of the influence of leptin on renal 1α‐hydroxylase mRNA expression in leptin‐deficient ob/ob mice. Exposure to leptin (200 ng/mL) for 24 hours stimulated FGF‐23 expression by primary cultured rat osteoblasts. Administration of leptin (4 mg/kg i.p. at 12‐hour intervals for 2 days) to ob/ob mice markedly increased the serum FGF‐23 concentration while significantly reducing the serum levels of calcium, phosphate, and 1α,25‐dihydroxyvitamin D₃ [1,25(OH)₂D₃]. Administration of FGF‐23 (5 µg i.p. at 12‐hour intervals for 2 days) to ob/ob mice suppressed renal 1α‐hydroxylase mRNA expression. The main site of FGF‐23 mRNA expression was the bone, and leptin markedly increased the FGF‐23 mRNA level in ob/ob mice. In addition, leptin significantly reduced 1α‐hydroxylase and sodium‐phosphate cotransporters (NaP_i‐IIa and NaP_i‐IIc) mRNA levels but did not affect Klotho mRNA expression in the kidneys of ob/ob mice. Furthermore, the serum FGF‐23 level and renal expression of 1α‐hydroxylase mRNA were not influenced by administration of leptin to leptin receptor–deficient (db/db) mice. These results indicate that leptin directly stimulates FGF‐23 synthesis by bone cells in ob/ob mice, suggesting that inhibition of renal 1,25(OH)₂D₃ synthesis in these mice is at least partly due to elevated bone production of FGF‐23. © 2010 American Society for Bone and Mineral Research     

北京地区中老年人FRAX骨折风险评估与BMD、骨代谢相关生化指标间的相关回归研究

目的探讨北京南郊地区中老年人FRAX评估未来10年全身骨折风险PMOF、骨密度BMD、骨代谢相关指标指标25(OH)D3、PTH、N-MID等在年龄、性别、体质指数之间的差异及变化趋势,研究PMOF、骨密度与各骨代谢相关生化指标之间的相关性。方法收集接受DXA桡骨远端骨密度(BMD)检查的体检人群1133例,代入FRAX骨折风险评估工具计算全身主要部位骨折概率(PMOF),收集相应骨代谢生化指标:25-羟维生素D3[25(OH)D_3],血清骨钙素N端中分子片段(N-MID),甲状旁腺素(PTH)、血钙(Ca)、血磷(P)、血清碱性磷酸酶(ALP)等。分析比较各指标随年龄的变化趋势,比较各年龄组各指标性别间差异;分析比较不同性别、各年龄组中各指标在不同体质指数之间的差异及其变化趋势;采用多元逐步回归法分别分析未来10年骨折风险概率(PMOF)、BMD与各因素、各生化指标之间的相关回归关系。结果非优势手臂桡骨远端1/3处骨密度BMD随年龄增长而降低,各年龄组男性BMD值均大于女性,PMOF随年龄增长而增加,各年龄组男性PMOF均小于女性,差异有统计学意义(P0.05);各年龄组25(OH)D_3水平男性均大于女性,50岁以上年龄组N-MID男性均小于女性,差异有统计学意义(P0.05);多元逐步回归分析中BMD与年龄、N-MID呈负相关,与BMI为正相关,男性大于女性;PMOF与BMD、年龄呈负相关,与BMI、N-MID呈正相关,男性小于女性;在不同性别、各年龄组中BMI正常组的PMOF最低,超重组最高,差异有统计学意义。其他生化指标与BMD、PMOF之间的相关关系不显著(P0.05)。结论 BMD、PMOF与性别、年龄、BMI、骨钙素均相关,其中女性OF的风险均高于男性;BMD随年龄增长而降低,骨折风险增加;BMD与BMI呈正相关,但PMOF表现为超重人群骨折风险最高,故超重亦是使骨折风险增加的危险因素。随血清骨钙素增高,BMD降低,骨折风险增高,可在一定程度上反映骨组织的新陈代谢情况。关注骨代谢生化指标变化可在一定程度上预判骨密度及PMOF水平,对骨质疏松及其骨折的的早发现、早诊断、早预防和早治疗提供一定参考及理论依据。     

25(OH) Vitamin D3 in patients with chronic kidney disease and those on dialysis: rediscovering its importance

In terms of both exogenous sources (diet), and endogenous production (activation through exposure to ultraviolet light), vitamin D is unique. Few foods naturally contain vitamin D and only a few are fortified with vitamin D. Most people get more than 90% of their vitamin D requirements from exposure to sunlight. Those who protect their skin from ultraviolet-B radiation with clothing or sunscreen, the elderly, and dark-skinned individuals have limited capacity to produce vitamin D. Vitamin D deficiency is common in the general population and even more common in patients with chronic renal failure (CKD). Increased use of sun-blocking agents and decreased exposure to sunlight, to reduce the risk of skin cancer, attributed to exposure to UV radiation, may contribute to the increase in vitamin D deficiency in the population. These issues are particularly important in the dialysis population who are at particular risk because these, mostly elderly, individuals have an inactive life style and have reduced exposure to sunshine and UV light, thus limiting the actinic synthesis of vitamin D. The nephrology community seems to have overlooked the importance of vitamin D for overall health and well being in patients with CKD. Recently however, several authors have called attention to the role of plasma 25(OH)D₃ levels in mineral metabolism dysregulation in patients with chronic kidney diseases, and those on dialysis. Vitamin D not only contributes to skeletal health but also plays a major role in the health of a wide variety of other organ systems. It seems that vitamin D supplementation is the most effective way of preventing vitamin D deficiency.