Effect of immobilization upon renal synthesis of 1,25-dihydroxyvitamin D in disabled elderly stroke patients

A 1,25-dihydroxyvitamin D [1,25-(OH)2D] deficiency and immobilization-related increased serum calcium concentration have been observed in hemiplegic stroke patients. To elucidate the influence of increased serum calcium concentration on bone metabolism, we measured serum biochemical indices and bone mineral density (BMD) in the second metacarpals of 170 elderly subjects with hemiplegic stroke and 72 age-matched healthy controls. Serum concentrations of 25-hydroxyvitamin D [25-(OH)D], 1,25-(OH)2D, ionized calcium, intact parathyroid hormone (PTH), intact bone Gla protein (BGP), and pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP) were measured. An increased serum calcium concentration (mean 2.543 mEq/L) was observed in this population and correlated negatively with the Barthel index (mean 66), indicating immobilization-induced bone resorption with consequent increased serum calcium. Decreased serum concentrations of 1,25-(OH)2D (mean 25.0 pg/mL) and serum 25-OHD concentration (mean 11.6 ng/mL) were noted. Serum PTH was not increased (mean 34.8 pmol/L). Serum levels of BGP were decreased significantly, whereas serum ICTP concentrations were elevated (mean 15.2 ng/mL). A strong negative correlation was seen between the serum calcium concentration and 1,25-(OH)2D (p < 0.0001). BMD of the second metacarpal in patients was decreased significantly compared with control subjects and highly correlated with 25-(OH)D and 1,25-(OH)2D concentrations. Immobilization-related increased serum calcium levels may inhibit PTH secretion, and thus 1,25-(OH)2D production. In addition, 25-(OH)D insufficiency also may contribute to decreased concentration of 1,25-(OH)2D.     

Etidronate for fracture prevention in amyotrophic lateral sclerosis: a randomized controlled trial

Incidence of fractures is high in patients with amyotrophic lateral sclerosis (ALS) as compared to age-matched healthy controls. Our previous cross-sectional study showed that immobilization-induced hypercalcemia (i.e., increased bone resorption) and 25-hydroxyvitamin D (25-OHD) deficiency contribute to reduced bone mineral density (BMD). This study aims to address the possibility that treatment with etidronate may reduce the bone resorption and lower the incidence of fractures in patients with ALS. ALS patients were randomly assigned to daily treatment with 400 mg of etidronate (n = 41) or a placebo (n = 41) and followed for 2 years. At baseline, both groups had low BMD with high levels of serum ionized calcium and pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen (ICTP). In the etidronate group, serum calcium and ICTP levels decreased significantly during the study period, while the levels in the placebo group were increased. Over 2 years, serum 25-OHD reduced to the potentially osteomalacic level (less than 5 mg/mL) in both groups. BMD decreased by 3.6% in the etidronate group and decreased by 12.1% in the placebo group (P < 0.0001). Fractures occurred in 7 patients in the placebo group and one patient in the risedronate group. The relative risk in the risedronate group as compared with the placebo group was 0.14 (95% confidence interval, 0.02 to 1.11). The number of fractures per 1000 patient-years was 14 and 92 for the etidronate and placebo groups, respectively. Treatment with etidronate prevents further loss of BMD in patients with ALS and leads to the prevention of fractures.     

Amelioration of osteoporosis by menatetrenone in elderly female Parkinson's disease patients with vitamin D deficiency

Significant reduction in bone mineral density (BMD) occurs in patients with Parkinson's disease (PD), correlating with immobilization and with vitamin D deficiency, and increasing the risk of hip fracture, especially in elderly women. As a biological indicator of compromised vitamin K status, an increased serum concentration of undercarboxylated osteocalcin (Oc) has been associated with reduced BMD in the hip and an increased risk of fracture in otherwise healthy elderly women. We evaluated treatment with vitamin K(2) (menatetrenone; MK-4) in maintaining BMD and reducing the incidence of nonvertebral fractures in elderly female patients with PD. In a random and prospective study of PD patients, 60 received 45 mg of MK-4 daily for 12 months, and the remaining 60 (untreated group) did not. At baseline, patients of both groups showed vitamin D and K(1) deficiencies, high serum levels of ionized calcium, and glutaminic residue (Glu) Oc, and low levels of parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D [1,25-(OH)(2)D], indicating that immobilization-induced hypercalcemia inhibits renal synthesis of 1,25-(OH)(2)D and compensatory PTH secretion. BMD in the second metacarpals increased by 0.9% in the treated group and decreased by 4.3% in the untreated group (p < 0.0001). Vitamin K(2) level increased by 259.8% in the treated group. Correspondingly, significant decreases in Glu Oc and calcium were observed in the treated group, in association with an increase in both PTH and 1,25-(OH)(2)D. Ten patients sustained fractures (eight at the hip and two at other sites) in the untreated group, and one hip fracture occurred among treated patients (p = 0.0082; odds ratio = 11.5). The treatment with MK-4 can increase the BMD of vitamin D- and K-deficient bone by increasing vitamin K concentration, and it can also decrease calcium levels through inhibition of bone resorption, resulting in an increase in 1,25-(OH)(2)D concentration.     

Changes in Bone and Calcium Metabolism Following Hip Fracture in Elderly Patients

Although hip fracture is one of the most common causes of acute immobilization in elderly patients, little is known about the influence of immobilization on changes in bone and calcium metabolism following this event. We therefore compared serum biochemical indices of bone and calcium metabolism in 20 elderly subjects with hip fracture with those measured in 20 healthy age-matched controls. Rankin scores, a measure of functional dependence with 0 representing independence and 5 representing total dependence, were assigned. We also examined serial changes in these biochemical indices from shortly following the fracture to the early recovery period. Ionized calcium, intact parathyroid hormone (PTH), intact bone Gla protein (BGP), pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP), 25-hydroxyvitamin D (25-OHD), and 1,25-dihydroxyvitamin D (1,25-[OH]₂D) were measured. One week after the fracture, mean serum concentrations of calcium and ICTP were elevated in correspondence to degree of immobilization (mean Rankin score; 4.4), while serum concentrations of BGP, PTH, 25-OHD, and 1,25-[OH]₂D were depressed. Rankin score (mean: 4.4) correlated positively with ICTP and negatively with BGP at this time. At 2 months, calcium and ICTP elevation decreased and BGP, PTH and 1,25-[OH]₂D were less depressed, coinciding with a decline in Rankin score from 4.2 to 2.2. Indices were further improved at 3 months (mean Rankin score, 1.3), with calcium and BGP returning to normal. We concluded that increased bone resorption, and decreased bone formation, and hypercalcemia are present by 1 week following the hip fracture, and some resorption increase persists for at least 3 months. These changes could explain in part the high risk of another hip fracture. Received: 3 April 2000 / Accepted: 15 December 2000     

Lack of relationship between parathyroid hormone and 1,25-dihydroxyvitamin D in chronic renal failure

In the present study, concentrations of parathyroid hormone (PTH), determined by an intact PTH assay and a midregion/C-terminal PTH assay, 1,25-dihydroxyvitamin D [1,25(OH)2D3], ionized calcium and phosphate were measured in 15 patients with a stable creatinine clearance (Ccr) of 21.2 +/- 14.4 ml/min (mean +/- SD; group 1) and in 10 patients with a Ccr regularly undergoing hemodialysis (group 2, Ccr not measured). In group 1, the mean concentration of 1,25(OH)2D3 was significantly increased compared with the level in group 2, whereas no differences were found concerning the concentrations of intact PTH, midregion/C-terminal PTH, ionized calcium and phosphate. In group 1, the PTH concentration correlated inversely with ionized calcium concentration and Ccr, which in turn, was directly correlated. The concentration of 1,25(OH)2D3 correlated inversely with phosphate concentration, but did not correlate with either PTH or ionized calcium concentrations. In group 2 no correlation was found between any of the biochemical variables. The data demonstrate that in patients with stable renal failure, the concentration of ionized calcium still regulates PTH secretion but other variables such as parathyroid cell mass and setpoint may interfere with the interrelation. The elevated concentration of phosphate in renal failure may override PTH as a regulator of the renal 1,25(OH)2D3 formation. The lack of correlation in the hemodialyzed patients may be attributed to extrarenal production of 1,25(OH)2D3, reduced binding of 1,25(OH)2D3 to parathyroid tissue or the major changes in calcium homeostasis caused by the hemodialysis.     

老年男性2型糖尿病患者各种钙调激素与骨密度改变的关系

目的测定老年男性2型糖尿病患者各种钙调激素及骨密度,探讨老年男性2型糖尿病患者骨质疏松的发病机理,为其防治提供理论依据。方法用双能X线吸收法测定70例老年男性2型糖尿病患者及60例年龄、体重指数相匹配的对照者的腰椎及髋部骨密度,并采用放免法测定血清骨钙索(BGP)、抗酒石酸酸性磷酸酶(TRAP)、甲状旁腺素(PTH)、降钙素(CT)、1,25(OH)2D3、25(OH)D3、尿羟脯氨酸(HOP)等,两组进行比较。结果 老年男性2型糖尿病患者较对照组骨密度显著降低。血BGP、CT、1,25(OH)2D3浓度低于对照组(P<0.05).TRAP、PTH、尿HOP显著高于对照组(P<0.05)。结论老年男性2型糖尿病患者PTH、CT、1,25(OH)2D3等钙调激素分泌及代谢失常,影响骨代谢,出现糖尿病性骨质疏松,表现为骨吸收增加,骨形成减少与缓慢,骨吸收过程大于骨形成。     

尿毒症患者桡动脉钙化与骨密度及血清骨代谢指标的关系

目的 观察尿毒症患者桡动脉钙化情况并分析其与骨密度及血清骨代谢指标改变的关系.方法 以67例尿毒症患者为对象,取内瘘手术切除的桡动脉段,von Kossa染色及透射电镜检测血管钙化情况;检测Scr、血钙、磷、甲状旁腺素(iPTH);测定腰椎、股骨颈骨密度(BMD);放射免疫法测定血清25羟维生素D3 (25OHD)、1,25羟维生素D3[1,25(OH) 2D];ELISA法测定成纤维生长因子(FGF) 23、骨特异性碱性磷酸酶(BAP)、骨钙素(BGP)与Ⅰ型胶原吡啶交联物(ICTP).以23例健康体检者为对照,仅接受血清及骨密度检查.结果 von Kossa染色见24例(35.8％)尿毒症患者桡动脉中膜明显钙沉积;电镜发现中膜平滑肌细胞由 收缩型向分泌型转化,胞内有较多含钙囊泡,基质胶原明显增加伴钙磷结晶附着,程度与钙化评分一致.与对照组比较,尿毒症患者血磷、iPTH、FGF23、BGP、ICTP显著增加(均P＜0.05),血钙、25OHD、1,25(OH)2D显著降低(均P＜0.01),腰椎、股骨颈BMD也显著降低(均P＜0.01).相关分析显示,桡动脉钙化与糖尿病、股骨颈及腰椎骨密度Z值、ICTP、FGF23相关(r=0.62、-0.43、-0.25、0.34、0.86,P=0.000、0.012、0.001、0.018、0.000),与iPTH无相关(r=-0.08,P=0.306).按iPTH水平分层后,低iPTH(＜150 ng/L)组、高iPTH(＞300 ng/L)组患者iPTH与钙化相关(r=-0.41、0.31,P=0.044、0.023).多元回归分析显示,股骨颈骨密度Z值、ICTP、FGF23是桡动脉钙化的独立危险因素(β=-0.221、0.181、0.260,P=0.021、0.024、0.036).结论 尿毒症桡动脉钙化与平滑肌细胞合成和分泌较多的含钙基质有关,骨密度降低、骨转化率异常、骨吸收增加、血清FGF23水平增加是其危险因素.     

Exogenous PTH and Endogenous 1,25‐Dihydroxyvitamin D Are Complementary in Inducing an Anabolic Effect on Bone

PTH and 1,25(OH)₂D each exert dual anabolic and catabolic skeletal effects. We assessed the potential interaction of PTH and 1,25(OH)₂D in promoting skeletal anabolism by comparing the capacity of exogenous, intermittently injected PTH(1‐34) to produce bone accrual in mice homozygous for the 1α(OH)ase‐null allele [1α(OH)ase^?/? mice] and in wildtype mice. In initial studies, 3‐mo‐old wildtype mice were either injected once daily (40 μg/kg) or infused continuously (120 μg/kg/d) with PTH(1–34) for up to 1 mo. Infused PTH reduced BMD, increased the bone resorption marker TRACP‐5b, and raised serum calcium but did not increase serum 1,25(OH)₂D. Injected PTH increased serum 1,25(OH)₂D and BMD, raised the bone formation marker osteocalcin more than did infused PTH, and did not produce sustained hypercalcemia as did PTH infusion. In subsequent studies, 3‐mo‐old 1α(OH)ase^?/? mice, raised on a rescue diet, and wildtype littermates were injected with PTH(1–34) (40 μg/kg) either once daily or three times daily for 1 mo. In 1α(OH)ase^?/? mice, baseline bone volume (BV/TV) and bone formation (BFR/BS) were lower than in wildtype mice. PTH administered intermittently increased BV/TV and BFR/BS in a dose‐dependent manner, but the increases were always less than in wildtype mice. These studies show that exogenous PTH administered continuously resorbs bone without raising endogenous 1,25(OH)₂D. Intermittently administered PTH can increase bone accrual in the absence of 1,25(OH)₂D, but 1,25(OH)₂D complements this PTH action. An increase in endogenous 1,25(OH)₂D may therefore facilitate an optimal skeletal anabolic response to PTH and may be relevant to the development of improved therapeutics for enhancing skeletal anabolism.     

Cholecalciferol Supplementation Attenuates Bone Loss in Incident Kidney Transplant Recipients: A Prespecified Secondary Endpoint Analysis of a Randomized Controlled Trial

Vitamin D deficiency, persistent hyperparathyroidism, and bone loss are common after kidney transplantation (KTx). However, limited evidence exists regarding the effects of cholecalciferol supplementation on parathyroid hormone (PTH) and bone loss after KTx. In this prespecified secondary endpoint analysis of a randomized controlled trial, we evaluated changes in PTH, bone metabolic markers, and bone mineral density (BMD). At 1 month post-transplant, we randomized 193 patients to an 11-month intervention with cholecalciferol (4000 IU/d) or placebo. The median baseline 25-hydroxyvitamin D (25[OH]D) level was 10 ng/mL and 44% of participants had osteopenia or osteoporosis. At the end of the study, the median 25(OH)D level was increased to 40 ng/mL in the cholecalciferol group and substantially unchanged in the placebo group. Compared with placebo, cholecalciferol significantly reduced whole PTH concentrations (between-group difference of −15%; 95% confidence interval [CI] −25 to −3), with greater treatment effects in subgroups with lower 25(OH)D, lower serum calcium, or higher estimated glomerular filtration rate (p_int < 0.05). The percent change in lumbar spine (LS) BMD from before KTx to 12 months post-transplant was −0.2% (95% CI −1.4 to 0.9) in the cholecalciferol group and −1.9% (95% CI −3.0 to −0.8) in the placebo group, with a significant between-group difference (1.7%; 95% CI 0.1 to 3.3). The beneficial effect of cholecalciferol on LS BMD was prominent in patients with low bone mass p_int < 0.05). Changes in serum calcium, phosphate, bone metabolic markers, and BMD at the distal radius were not different between groups. In mediation analyses, change in whole PTH levels explained 39% of treatment effects on BMD change. In conclusion, 4000 IU/d cholecalciferol significantly reduced PTH levels and attenuated LS BMD loss after KTx. This regimen has the potential to eliminate vitamin D deficiency and provides beneficial effects on bone health even under glucocorticoid treatment. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).     

Biochemical parameters associated with low bone density in healthy men and women.

A causal role in age-related bone loss has been attributed to alterations in vitamin D status, the bone mineral regulating hormones, and/or renal function. We assessed biochemical parameters of bone metabolism and renal function in healthy subsets of young and old men (n = 191) and women (n = 120) and evaluated the relationships between these parameters and bone mineral density (BMD) in the radius, spine, and femur. There were no significant associations between BMD at any site and serum 25-OHD, 1,25-(OH)2D, PTH, or creatinine clearance in either young men or in young or old women, after controlling for age. In old men, however, lower radius BMD was significantly related to higher PTH and higher 1,25-(OH)2D and marginally related to lower 25-OHD values. In young men, there were unexpected but significant associations between lower femoral neck BMD and higher serum osteocalcin and urinary calcium/creatinine excretion after age adjustment. In old women, lower spine and radius BMD was also significantly correlated with higher serum osteocalcin. In this healthy, vitamin D-replete population, there were significant cross-sectional declines in BMD in the femur in young and old men and at all sites in old women. Elevated remodeling may be an important feature that contributes to reduced femoral BMD in young men and reduced spine and radius BMD in old women. However, compromised renal function or levels of 1,25-(OH)2D or elevated PTH appear to be neither necessary nor relevant as determinants of osteopenia in the spine or femur in these normal, healthy men and women.     

The relationship of vitamin D status to bone mineral density in an Italian population of postmenopausal women

Several authors have found a relationship between vitamin D status and bone mineral density (BMD). To our knowledge, no previous studies on this topic have been carried out on the Italian postmenopausal population. We studied this relationship retrospectively in 156 Italian postmenopausal women. We also investigated the relationship between parathyroid hormone (PTH) and BMD. Measurements of BMD were taken at the lumbar spine and upper femur by dual X-ray absorptiometry. Serum 25(OH)D (calcidiol), 1,25(OH)2D (calcitriol), PTH, calcium, phosphorus, creatinine, osteocalcin and urinary calcium and phosphorus were measured according to the current laboratory methods of analysis. We found a positive statistically significant correlation between BMD, both at the spine and hip, and 25(OH)D, and a negative statistically significant correlation between BMD and PTH. No statistically significant correlation was found between BMD and 1,25(OH)2D. Crude logistic regression showed age, 25(OH)D and PTH were significant predictors of low BMD, while 1,25(OH)2D was not. Backward logistic regression showed 25(OH)D was the best predictive model for spine osteoporosis together with age, and on its own it was the best predictive model for femoral neck osteoporosis.No funding sources supported this publication.     

Hip bone loss is attenuated with 1000 IU but not 400 IU daily vitamin D3: A 1‐year double‐blind RCT in postmenopausal women

Few year‐long vitamin D supplementation trials exist that match seasonal changes. The aim of this study was to determine whether daily oral vitamin D₃ at 400 IU or 1000 IU compared with placebo affects annual bone mineral density (BMD) change in postmenopausal women in a 1‐year double‐blind placebo controlled trial in Scotland. White women aged 60 to 70 years (n = 305) were randomized to one of two doses of vitamin D or placebo. All participants started simultaneously in January/February 2009, attending visits at bimonthly intervals with 265 (87%) women attending the final visit and an additional visit 1 month after treatment cessation. BMD (Lunar iDXA) and 1,25‐dihydroxyvitamin D[1,25(OH)₂D], N‐terminal propeptide of type 1 collagen [P1NP], C‐terminal telopeptide of type I collagen [CTX], and fibroblast growth factor‐23 [FGF23] were measured by immunoassay at the start and end of treatment. Circulating PTH, serum Ca, and total 25‐hydroxyvitamin D [25(OH)D] (latter by tandem mass spectrometry) were measured at each visit. Mean BMD loss at the hip was significantly less for the 1000 IU vitamin D group (0.05% ± 1.46%) compared with the 400 IU vitamin D or placebo groups (0.57% ± 1.33% and 0.60% ± 1.67%, respectively) (p < 0.05). Mean (± SD) baseline 25(OH)D was 33.8 ± 14.6 nmol/L; comparative 25(OH)D change for the placebo, 400 IU, and 1000 IU vitamin D groups was ?4.1 ± 11.5 nmol/L, +31.6 ± 19.8 nmol/L, and +42.6 ± 18.9 nmol/L, respectively. Treatment did not change markers of bone metabolism, except for a small reduction in PTH and an increase in serum calcium (latter with 1000 IU dose only). The discordance between the incremental increase in 25(OH)D between the 400 IU and 1000 IU vitamin D and effect on BMD suggests that 25(OH)D may not accurately reflect clinical outcome, nor how much vitamin D is being stored. © 2013 American Society for Bone and Mineral Research.     

Calciotropic hormones in elderly people with and without hip fracture

The effects of age on calciotropic hormones are not completely understood. The presence of secondary hyperparathyroidism has previously been demonstrated, particularly in patients with hip fracture. The role of a disturbance of vitamin D metabolism, especially a defect in l-hydroxylation, is debated. The aim of this study was to compare serum parathyroid hormone (PTH), osteocalcin and vitamin D metabolites (25(OH)D and 1,25(OH)2D) in osteoporotic elderly patients with hip fracture (HF) and in elderly controls. We studied 57 HF patients aged 83.9±5.9 years (mean±SD) and 68 controls aged 82.5±5 years recruited during two periods: 1 January and 30 April 1988 and 1989. Patients with chronic renal failure (serum creatinine above 150, µmol/l), cancer, or other metabolic bone disease were excluded. Thirty healthy young adults were studied in 1989 only for measurement of 1,25(OH)2D. (1,25(OH)2D was measured by different laboratories in 1988 and 1989 for technical reasons.) We also measured serum PTH, osteocalcin, total calcium and ionized calcium. 1,25(OH)2D levels were not statistically different between HF patients and controls for the two years, nor between HF patients and young healthy adults in 1989. 25(OH)D was decreased in HF patients (p<0.003), as was ionized calcium. Serum PTH levels were higher in HF patients than in controls (p<0.01). A positive correlation has been found between PTH and age in HF patients (r=0.29;p<0.03) and in the whole group of HF patients and controls. There was a significant decrease in osteocalcin in HF patients versus elderly controls (p<0.04). Our results confirm the high levels of intact PTH in elderly HF patients, this elevation of PTH being known to increase bone resporption. Low serum osteocalcin in HF patients seems to reflect decreased bone formation. Thus, this association contributes to the accelerated bone loss in hip fracture. This study also suggests that 1,25(OH)2D is not significantly lowered in case of hip fracture, and l-hydroxylase is not deficient, in spite of a lack of the substrate of this enzyme (25(OH)D). Therefore, a defect of 1,25(OH)2D does not appear to be a pathogenetic factor in bone aging.     

Regulation of 1,25-dihydroxyvitamin D3 by calcium in the parathyroidectomized, parathyroid hormone-replete rat

Parathyroid hormone (PTH) is a major stimulus for the renal production of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]. Elevated arterial blood ionized calcium ([Ca2+]) depresses serum 1,25-(OH)2D3 in nonparathyroidectomized rats even when serum PTH is maintained at high levels by infusion. However, suppression by [Ca2+] of endogenous PTH, causing the fall in 1,25-(OH)2D, cannot be excluded. To determine whether [Ca2+] regulates 1,25-(OH)2D3 in the absence of a variation in PTH, we parathyroidectomized (PTX) rats (post-PTX calcium levels less than 7.0 mg/dl), inserted arterial and venous catheters, and then replaced PTH using an osmotic pump. We varied [Ca2+] by infusing either 75 mM sodium chloride (control), 0.61 mumol/min of EGTA (EGTA), or calcium chloride at 0.61 mumol/min (low calcium) or 1.22 mumol/min (high calcium) for 24 h 5 days after surgery. Blood was then drawn from the rat through the arterial catheter. Compared with the control, [Ca2+] fell with EGTA, remained constant with the low-calcium infusion, and rose with the high-calcium infusion. 1,25-(OH)2D3 was correlated inversely with [Ca2+] in all four groups together (r = -0.635, n = 34, p less than 0.001), within the control group alone (r = -0.769, n = 11, p less than 0.002), and within the EGTA group alone (r = -0.774, n = 10, p less than 0.003). Serum phosphorus, PTH, and arterial blood pH were not different in any group, and none correlated with serum 1,25-(OH)2D3. We conclude that 1,25-(OH)2D3 levels are regulated by [Ca2+] independently of serum PTH, phosphorus, and acid-base status, all of which support the hypothesis that [Ca2+] is a principal regulator of serum 1,25-(OH)2D3 in the rat.     

Remarkable increase in lumbar spine bone mineral density and amelioration in biochemical markers of bone turnover after parathyroidectomy in elderly patients with primary hyperparathyroidism: a 5-year follow-up study

We evaluated the efficacy of parathyroidectomy (PTX) on bone mineral density (BMD) and hormonal and biochemical markers of bone metabolism in elderly primary hyperparathyroidism (PHPT) patients, and followed these patients for 5 years after PTX. Eleven PHPT patients were enrolled and were followed for 5 years by measuring lumbar spine BMD (LSBMD), femoral BMD (FBMD), radial BMD (RBMD), parathyroid hormone (PTH), 1,25-dihydroxyvitamin D [1,25(OH)₂D], serum calcium (SCa), inorganic phosphate (iP), bone-specific alkaline phosphatase (BAP), intact osteocalcin (IOC), urinary excretion of type I collagen cross-linked N-telopeptide (NTx), and urinary deoxypyridinoline (DPD). PTX produced significant increases in LSBMD of 12%, 19%, and 29% as compared with pretreatment levels after 1, 3, and 5 years, respectively (P < 0.01, compared to baseline), whereas there was no significant increase in FBMD and a slight decrease in RBMD. SCa and iP levels remained normal over the five years. PTX also resulted in significant decreases in PTH, 1,25(OH)₂D, BAP, IOC, NTx, and DPD that continued for at least 3 years after PTX. In conclusion, PTX seemed effective to normalize various markers of bone metabolism in elderly PHPT patients and is recommended to patients with low LSBMD to prevent future fractures. On the other hand, the use of PTX for low FBMD or RBMD patients requires further discussion.     

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.     

Abnormal calcium homeostasis in disabled stroke patients with low 25-hydroxyvitamin D

Disabled elderly stroke patients occasionally have very low serum 25-hydroxyvitamin D (25-OHD), which may be due to sunlight deprivation and malnutrition. Many of such patients have very low level of serum 1, 25-dihydroxyvitamin D (1, 25-[OH]2D; calcitriol), and immobilization-induced hypercalcemia may be responsible for inhibition of renal synthesis of calcitriol. To elucidate determinants of serum 1, 25-[OH]2D levels in elderly poststroke patients, we measured serum indices of bone and calcium metabolism and metacarpal bone mineral density (BMD). Patients whose serum 1, 25-[OH]2D concentration was below the mean-3 SD of normal control subjects were defined as the low 1, 25-[OH]2D group and the rest of the patients were designated as the normal group. Mean illness duration was 59 months in the normal group and 20 months in the low group. The Barthel index (BI), which predicts the degree of immobilization, was significantly lower in the low group than in the normal group. Mean serum 1, 25-[OH]2D and 25-OHD concentrations in the normal group were 36.7 pg/ml and 4.4 ng/ml, respectively; and those in the low group were 14.2 pg/ml and 1.8 ng/ml, respectively. Multiple regression analysis identified illness duration and calcium level as independent determinants of 1, 25-[OH]2D in both groups, and PTH in the normal group and 25-OHD in the low group were additional independent determinants. BMD in stroke patients was significantly lower than that in controls, and BMD in the normal group was lower as compared to the low group. BMD correlated negatively with 1, 25-[OH]2D and PTH in the normal group, and hyperparathyroidism may contribute to reduced BMD. These results suggest that treatment of decreased bone mass in stroke patients has to be individualized according to vitamin D status and calcium homeostasis.     

慢性肝病患者血清VitD3水平与骨代谢的关系

检测了部分慢性乙型肝炎（下简称慢乙肝）及肝硬化患者的血清1，25（OH）2D3，骨钙素（BGP），甲状旁腺素（PTH），钙，磷及尺桡平均密度（BMD），并与对照组比较，结果两组患者血清1，25（OH）2D3，BGP及BMD值均明显下降，肝硬化组下降尤为显著，肝硬化组血清PTH显著升高，两组患者血钙明显降低，而血磷三组间无差异，1，5（OH）2D3水平与BGP，BMD呈显著正相关；PTH与血钙，BMD无相关性。提示慢性肝病患者存在以骨形成减少为主的骨代谢紊乱，其中血清1，25（OH）2D3减少为关键因素，PTH虽升高，但与肝病患者骨密度变化无相关。     

Regulation of calcium absorption by 1,25,dihydroxy-vitamin D--studies of the effects of a bisphosphonate treatment

In 10 patients with Paget's disease of bone and 2 patients with osteoporosis, we studied the effects of hypocalcemia and hypophosphatemia induced by disodium-(3-amino-1-hydroxypropylidene)-1,-bisphosphonate (APD) treatment on the serum concentration of PTH and 1,25-dihydroxy-vitamin D [1,25(OH)2D3] and on calcium absorption and balance. The fall in serum calcium and phosphate was associated with a rise in the serum concentration of PTH and 1,25(OH)2D3, coupled with increases in net calcium absorption and calcium balance. The concentration of 1,25(OH)2D3 was significantly related (P less than 0.001) to the serum calcium (r = 0.66), the serum phosphate (r = 0.78), and the serum PTH (r = 0.71), confirming the interrelated control of these parameters on 1,25(OH)2D3 production. Moreover the rise in 1,25(OH)2D3 caused an appropriate rise in calcium absorption (r = 0.74) and calcium balance (r = 0.86), showing that this vitamin D metabolite contributes as a hormone to calcium homeostasis.