The clinical significance of serum osteocalcin and N-terminal propeptide of type I collagen in predialysis patients with chronic renal failure

Several new serum markers for bone metabolism have recently become available and are being applied to clinical practice. Their clinical usefulness in predialysis patients with chronic renal failure (CRF), however, has not yet been determined. Serum levels of three bone formation markers—bone alkaline phosphatase (BAP), osteocalcin (OC), and N-terminal propeptide of type I collagen (PINP)—and three bone resorption markers—type I collagen cross-linked N-telopeptide (NTx), deoxypyridinoline (DPD), and pyridinoline (PYD)—were measured simultaneously in 85 predialysis CRF patients (serum creatinine 3.5 ± 1.9 mg/dl, 61.0 ± 10.9 years old, 54 males and 31 females, 36 diabetics and 49 nondiabetics) to examine the relationships between these markers and bone mineral density (BMD) of the distal radius, as measured by peripheral quantitative computed tomography (pQCT). Trabecular BMD, which is strongly affected by bone metabolism, was significantly negatively correlated with each of the bone formation markers (r=–0.341, p=0.0016, for OC; r=–0.314, p=0.0036, for PINP; r=–0.238, p=0.0315, for BAP), but there was no significant correlation between BMD and any of the bone resorption markers. In multivariate regression analyses (adjusted by age, sex, presence of diabetes, glomerular filtration rate, intact parathyroid hormone, calcium, phosphate, and 1,25-dihydroxyvitamin D), OC and PINP were significantly associated with a decrease in BMD, but BAP was not. In conclusion, we demonstrated that in predialysis CRF patients, BMD of the distal radius, particularly of trabecular bone, is associated with serum OC and PINP levels. OC and PINP are suggested to be possible parameters for the clinical evaluation of the effect of bone metabolism on BMD.     

Vitamin D status and its relationship with bone mineral density in healthy Asian Indians

Synthesis of vitamin D takes place in the skin under the effect of sunlight. The Indian subcontinent is situated between 8.4° N and 37.6° N latitudes and has adequate sunshine throughout the year. Thus, it has been presumed that Indians are vitamin D sufficient. We measured serum 25-hydroxy vitamin D [25(OH)D] (n=92) and 1,25-dihydroxy vitamin D [1, 25(OH)₂D] (n=65) levels in healthy hospital staff, using ¹²⁵I radioimmunoassay. Serum intact parathyroid hormone (PTH) concentration was estimated by immunoradiometric assay. Bone mineral density was estimated using a dual energy X-ray absorptiometer (Hologic^R QDR 4500A). Using a serum 25(OH)D level of 15 ng/ml as a cutoff, 66.3% (61/92) of the subjects were found to be vitamin D deficient. Of these, 20.6% (19/92) subjects had severe vitamin D deficiency (<5 ng/ml), 27.2% (25/92) had moderate vitamin D deficiency (5–9.9 ng/ml), while 18.5% (17/92) had mild vitamin D deficiency (10–14.9 ng/ml). When a serum 25(OH)D level of 20 ng/ml was used as a cutoff, 78.3% subjects were diagnosed to be vitamin D deficient/insufficient. The serum 1,25(OH)₂D level was within the normal range (40.6±20.1 pg/ml; mean ± SD). Mean (±SD) serum intact PTH, estimated in a limited number of subjects (n=15), was 72.3 (±21.0) pg/ml (range 36–100 pg/ml). There was a significant correlation between daily sun exposure and 25(OH)D levels (r=0.731, P<0.001). The serum 25(OH)D level correlated with BMD at the femoral neck and Ward's triangle (r=0.50, P=0.020 and r=0.46, P=0.037, respectively). Our findings show that vitamin D deficiency is common in urban north Indian hospital staff. The possible reasons include inadequate sunlight exposure and skin pigmentation in Indians. The serum 1,25(OH)₂D level is not a good indicator of vitamin D deficiency. A low serum 25(OH)D level is possibly one of the reasons for lower bone mineral density among Indians.     

Bone mineral density and bone turnover markers in children with chronic renal failure

Bone mineral density (BMD) at lumbar spine (L₂-L₄) was measured by dual-energy X-ray absorptiometry (DEXA) in 21 children with predialysis chronic renal failure (CRF) and 44 children with end-stage renal failure (ESRF) on regular hemodialysis. BMD results were expressed as Z-scores. Osteopenia was documented in 13 predialysis patients (61.9%) and 26 patients (59.1%) with ESRF. No significant correlation was observed between Z-scores and the duration of CRF or estimated creatinine clearance. In osteopenic children there was a negative correlation between Z-scores and serum phosphorus (r=–0.61, P=0.004), intact parathyroid hormone (iPTH) (r=–0.47, P=0.03), and bone-specific alkaline phosphatase (r=–0.52, P=0.02) and a positive correlation with total calcium (r=0.41, P=0.07) and 25-hydroxycholecalciferol (r=0.53, P=0.02). Osteopenic children who had iPTH values 200 pg/ml were more osteopenic than those who had lower iPTH levels (P=0.006). In conclusion, osteopenia, assessed by DEXA, is frequent in children with CRF. It occurs early irrespective of the duration or the severity of CRF. In children with ESRF the degree of osteopenia is correlated with laboratory markers of renal osteodystrophy and patients with biochemical findings of secondary hyperparathyroidism are more osteopenic than the others.     

Influence of PTH and 1,25(OH)2D on calcium homeostasis and bone mineral content after gastric surgery

Summary In 57 patients surgically treated for ulcer, we found low 25OHD concentrations, elevated 1,25(OH)₂D concentrations, (P<0.001), a normal iPTH level, and a not significantly reduced bone mineral content (BMC) measured by single photon absorptiometry. The 25OHD concentrations were highest in patients regularly taking tablets containing vitamin D (P<0.05), whereas the 1,25 (OH)₂D concentrations and the BMC values were not affected by vitamin D intake. The most severe calcium metabolic disturbances were seen in 15 Billroth I resected patients whose BMC was 89.4±12.4% of normal. Although the dietary intake of calcium and vitamin D complied with the Scandinavian recommendations and calcium absorption was in the lower part of the normal range, the general state of nutrition appears to influence the bone mass of such patients. In the patients as a group, the 1,25(OH)₂D concentrations were significantly related to BMC (r=0.42,P<0.001) and biochemical signs of bone resorption (r=0.68,P<0.001) and formation (r=0.42,P<0.001) Conversely, no relationship could be detected between serum iPTH and bone mass or bone turnover. We suggest that the high 1,25(OH)₂D concentrations found after gastric resections express a compensatory process leading to an increase in calcium absorption, and that the initial event in this sequence is a trend toward low serum calcium levels. With increased demands on this regulation or lack of precursor for 1,25(OH)₂D synthesis, bone mass declines through the action of 1,25(OH)₂D and/or PTH.     

Threshold value of serum 25-hydroxyvitamin D concentration in relation to elevated serum parathyroid hormone concentrations in elderly Japanese women

This study was designed to determine the threshold value for 25-hydroxyvitamin D [25(OH)D] concentration in relation to elevated serum parathyroid hormone (PTH) concentrations in elderly Japanese women. The subjects were 582 noninstitutionalized, ambulant women who lived in a community in Japan. Serum 25(OH)D concentrations were determined using the Nichols Advantage chemiluminescent assay, and serum intact PTH concentrations were determined with a two-site immunoradiometric assay. Demographic characteristics, calcium intake, and serum 1,25(OH)₂D levels were also determined. The average age, body mass index (BMI), and calcium intake of the subjects were 74.5 years (SD 4.5), 23.3 kg/m² (SD 3.4), and 579 mg/day (SD 248), respectively. The serum log-transformed intact PTH concentration was significantly predicted by the serum 25(OH)D concentration (r = −0.147, P = 0.0004), but not by age, BMI, the serum log-transformed 1,25(OH)₂D concentration, or the log-transformed calcium intake. Analysis of variance with Dunnett's multiple comparisons showed that mean serum intact PTH concentrations with serum 25(OH)D concentrations less than 30 nmol/l (mean intact PTH = 5.89 pmol/l, P < 0.0001) and in the range 30–39 nmol/l (mean intact PTH = 4.54 pmol/l, P = 0.0067) were significantly higher than mean intact PTH concentrations for serum 25(OH)D concentrations greater than 50 nmol/l (mean intact PTH = 3.65 pmol/l, the baseline level), but the mean serum intact PTH concentration for 25(OH)D concentrations in the range 40–49 nmol/l (mean intact PTH = 3.70 pmol/l, P = 0.9975) was not. We conclude that serum 25(OH)D for ambulant elderly Japanese women should be maintained at 40 nmol/l or higher.     

Association of increased active PTH(1–84) fraction with decreased GFR and serum Ca in predialysis CRF patients: modulation by serum 25-OH-D

Summary As the serum calcium and glomerular filtration rate decreased, the proportion of active PTH(1–84) molecules in PTH immunoreactivity increased in serum from predialysis uremic patients, particularly those with vitamin D insufficiency. Introduction The PTH(1–84) fraction was altered in predialysis patients with chronic renal failure (CRF). Methods Serum PTH in predialysis CRF patients without any medication was measured by PTH(1–84)-specific whole PTH assay and intact PTH assay cross-reacting with N-truncated PTH. Results In CRF patients, the glomerular filtration rate (GFR) correlated positively with serum Ca and 1,25-dihydroxyvitamin D (1,25(OH)₂D), and inversely with serum Pi, log intact PTH, and log whole PTH. In multiple regression analysis, including age, gender, body mass index, GFR, Ca, and Pi and 1,25(OH)₂D as independent variables, serum Ca and GFR associated significantly with serum log whole PTH and intact PTH. Serum log whole PTH/intact PTH ratio, which increased as serum Ca and GFR decreased, retained a negative correlation in those with serum 25-hydroxyvitamin D levels below 20 ng/ml, but not in those above 20 ng/ml. The ratio also correlated positively with serum log tartrate-resistant acid-phosphatase-5b, log cross-linked N-telopeptide of type-I collagen, and log bone alkaline-phosphatase. Conclusion As GFR declined with suppression of serum Ca, the proportion of active PTH molecules increased in predialysis CRF patients, particularly those with vitamin D insufficiency.     

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

Summary 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-dihydroxyvitamin 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<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.     

Effects of oral phosphorus supplementation on mineral metabolism of renal transplant recipients

Background. Persistent hyperparathyroidism (HPT) is frequently observed in kidney transplant recipients. Hypophosphataemia is a common biochemical consequence of HPT. Theoretically, oral phosphorus administration may induce negative effects on the control of HPT, though this point has never been demonstrated in kidney-transplant recipients. This study was designed to evaluate the effects of oral phosphorus supplementation on the mineral metabolism of successful kidney transplant recipients. Methods. Thirty-two kidney transplant recipients with serum creatinine <2 mg/dl and serum phosphate levels <3.5 mg/dl were included in the study. After a wash-out period in which oral phosphorus supplementation was discontinued, the following parameters were determined (F0 period): serum calcium, phosphate, alkaline phosphatase, uric acid, bicarbonate, PTH, 1,25-dihydroxyvitamin D3 (1,25(OH)2D) and 25-hydroxyvitamin D3 (250HD). Creatinine clearance, calcium, and phosphate excretion were determined from a 24-h urine sample. The same determinations were repeated (F1 period) after all patients received 1.5 g of oral phosphorus for 15 days. For data analysis, patients were divided into two subgroups (optimal and suboptimal) according to allograft function (Ccr>or<70 ml/min/1.73 m²). Results. In the F0 period, only nine of 32 patients had PTH levels within the normal range (<65 pg/ml). The mean concentrations of PTH, 1,25(OH)2D and 25OHD were 132±97 pg/ml, 40.5+16 pg/ml and 12.5±8.2 ng/ml respectively. Phosphorus supplementation led to significant reductions in serum calcium and 1,25(OH)2D concentrations, as well as in urinary calcium excretion in the whole group. On the contrary, serum phosphate, PTH, and urinary phosphate excretion increased significantly. The percentage increase in PTH concentrations after phosphorus supplementation were similar in patients with optimal and suboptimal allograft function (33 vs 36%). The reduction of 1,25(OH)2D concentrations after phosphorus supplementation was observed mainly in the subgroup with optimal allograft function (21% reduction with respect to baseline values), while the mean 1,25(OH)2D concentrations in patients with suboptimal allograft function scarcely changed (1.4% increase). Changes in 1,25(OH)2D concentrations after phosphorus supplementation, expressed as a percentage of the initial concentrations, correlated positively with the percentage changes in PTH concentrations for the whole group, as well as for each subgroup. The best determinants for the percentage and the absolute increase in PTH concentration after phosphorus supplementation was the final serum phosphate concentration (F=4.84, r=0.37, P=0.035) and the increase in serum phosphate (F=7.69, r=0.45, P=0.009) respectively. Conclusions. Oral phosphorus supplementation led to a significant increase in the PTH concentration of kidney transplant recipients. The mean 1,25(OH)2D concentration decreased mainly in recipients with optimal allograft function. The counterbalance effect of PTH on 1,25(OH)2D production may account for the relative preservation of 1,25(OH)2D levels in recipients with suboptimal allograft function.     

Calcium regulating hormones and bone mineral content in patients after subtotal gastrectomy

Twenty-nine men who had undergone Billroth I gastrectomy and 19 men who had undergone Billroth II gastrectomy were studied to examine the changes in their calcium regulating hormones and bone mineral content following surgery. The serum calcium and phosphate concentrations in the patients with Billroth I and Billroth II were normal. The Billroth II group had an elevated level of serum alkaline phosphatase and reduced bone mineral content. The 24,25(OH)₂D concentration was reduced (P<0.01) and 25(OH)D and 1,25(OH)₂D concentrations were increased (P<0.01,P<0.05, respectively) in the Billroth II group. It was suggested by our study that the Billroth II patients had a reduced bone mineral content and an elevated 1,25(OH)₂D concentration. Therefore, the pathophysiology of postgastrectomy bone metabolic disease is not due to vitamin D deficiency, but may instead be due to reduced calcium absorption in the intestine.     

A longitudinal study for femoral neck bone mineral density increases in premenopausal caddies using dual-energy X-ray absorptiometry

This longitudinal study examined whether bone mineral density (BMD) of the lumbar spine and proximal femur is maintained in premenopausal caddies (n = 6; mean age 37.8 years) in comparison with desk workers (n = 6; mean age 40.8 years) at the same golf club. BMD was followed for 12 months using dual-energy X-ray absorptiometry (DXA) and bone metabolic markers and athletic ability were also examined. Longitudinally, for caddies, the change per year in BMD of the lumbar spine was +0.009 g/cm², while that of the proximal femur was +0.022 g/cm², showing significant differences (P < 0.05 by signed-rank test). Their athletic ability, in terms of leg-press power, also significantly increased, whereas bone metabolic markers, such as serum alkaline phosphatase, 1,25-(OH)₂ vitamin D₃, parathyroid hormone and the deoxypyridiniline/creatinine ratio, did not show significant changes. For desk workers, the change per year in BMD of the lumbar spine was +0.011 g/cm², while that of the proximal femur was −0.006 g/cm². Their BMD, athletic ability and bone metabolic markers did not show significant changes. These findings support the results of our previous study, that premenopausal women can achieve continuous gain in femoral neck BMD by regular intense athletic activity, and suggest that this is also true by the continuous extensive walking of golf caddies. Received: May 17, 2000 / Accepted: August 22, 2000     

Influence of age on effects of endogenous 1,25-dihydroxyvitamin D on calcium absorption in normal women

Recent reports of increases in serum 1,25-dihydroxyvitamin D [1,25(OH₂)D] concentration with aging despite no changes or decreases in calcium absorption suggest that elderly women have intestinal resistance to vitamin D action. Thus, in 15 young adult (30±1 year) and 15 elderly (74±1 year) women (mean±SE), we assessed the responsiveness of intestinal calcium absorption to increases in circulating 1,25(OH)₂D induced by 4 days of an experimental diet (150 mg calcium and 1600 mg phosphorus daily). True fractional calcium absorption (FCA) (⁴⁴Ca mixed with food and ⁴²Ca given intravenously, then their ratio in urine measured by mass spectrometry) was determined. Baseline serum intact parathyroid hormone (PTH) concentration was higher in the older women (P=0.01) whereas serum 1,25(OH)₂D concentration and true FCA were similar. In both groups, serum 1,25(OH)₂D concentrations increased (P<0.002) on the experimental diet. After 4 days on the diet, serum 1,25(OH)₂D increased over baseline by 30.5 and 35.6% and, despite these increases, true FCA was 40±3 versus 40±4%/24 hours (NS between groups) in the young and elderly women, respectively. These data suggest that either elderly women have normal intestinal responsiveness to vitamin D or that the resistance to it is too mild to be detected by these methods.     

Effect of declining renal function on bone density in aging women

Summary The factors that are responsible for trabecular bone loss in aging women are not completely understood. To evaluate declining renal function as a possible factor, we studied 19 Caucasian women (average age 67) who were from 6 to 41 years postmenopausal. Trabecular bone density was quantitated by computerized tomography of the spine. Serum calcium, phosphorus, and creatinine were normal in all subjects. Creatinine clearance averaged 74 ml/min (range 38–122), decreased with age (r=−0.60,P=0.003), and was inversely related to serum creatinine (r=−0.51,P=0.01). Bivariate regression demonstrated that bone density decreased with age (r=−0.59,P=0.004); controlling for the effect of creatinine clearance weakened this correlation to r=−0.45 (P=0.03); controlling additionally for 1,25-dihydroxyvitamin D [1,25(OH)₂D] and parathyroid hormone (PTH) reduced the correlation coefficient to r=−0.34 (P=0.11). Bone density also decreased in direct proportion to the decrement in creatinine clearance (r=0.44,P=0.03); controlling for the effects of 1,25(OH)₂D and PTH reduced this correlation coefficient to r=0.34 (P=0.11). These results suggest that occult renal insufficiency may contribute to bone loss in aging women, and that this effect may be mediated in part by 1,25(OH)₂D and PTH. In this age group renal function should be assessed by measuring creatinine clearance rather than the serum creatinine concentration since renal insufficiency can be masked by apparently normal circulating creatinine levels.     

The effect of endogenous estrogen fluctuation on metabolism of 25-hydroxyvitamin D

Summary To test the hypothesis that estrogen modulates the metabolism of 25-hydroxyvitamin D (25(OH)D) to 1,25-dihydroxyvitamin D (1,25(OH)₂D) and 24, 25-dihydroxyvitamin D (24, 25(OH)₂D), we studied 20 normal premenopausal women at four consecutive weekly intervals during one menstrual cycle. Estrogen stimulation was semiquantitatively defined into baseline, lowgrade, or medium-grade categories, based on endogenous estrone and estradiol concentrations. 1,25(OH)₂D increased incrementally from baseline levels of 34±3(SE) pg/ml to 39±3 pg/ml (P=0.2) with low-grade estrogen stimulation and to 43±3 pg/ml (P<0.05) with medium-grade estrogen stimulation, while 25(OH)D, 24,25(OH)₂D, vitamin D binding protein, parathyroid hormone, calcium, and phosphate did not change. 24,25(OH)₂D was correlated to 25(OH)D at baseline (r=0.65,P<0.01) and with low-grade estrogen stimulation (r=0.062,P<0.01), but not with medium-grade stimulation (r=0.13); these relationships are consistent with the concepts that 25(OH)D is metabolized predominantly to 24,25(OH)₂D at low estrogen levels, but not at higher estrogen levels. We conclude that endogenous estrogen elevation promotes formation of 1,25(OH)₂D from 25(OH)D, and that it may reciprocally inhibit synthesis of 24,25(OH)₂D.     

Comparison of vitamin D metabolism in early healthy and late osteoporotic postmenopausal women

Summary We studied 20 healthy premenopausal women aged 36.5±4.0 years (mean±1 SD), 123 healthy postmenopausal women aged 50.0±2.4 years, and 103 postmenopausal women aged 65.1±5.6 years with symptomatic osteoporosis (forearm and spinal fracture). Serum levels of vitamin D metabolites [25(OH)D, 24,25(OH)₂D₃, and 1,25(OH)₂D] were compared with (1) bone mass in the forearm (single photon absorptiometry) and in the spine (dual photon absorptiometry); (2) biochemical indices of bone formation (serum alkaline phosphatase, plasma bone Gla protien), and bone resorption (fasting urinary hydroxyproline); and (3) other biochemical estimates of calcium metabolism (serum calcium, serum phosphate, 24-hour urinary calcium, intestinal absorption of calcium). The present study revealed no difference in any of the vitamin D metabolites between the premenopausal women, the healthy postmenopausal women and the osteoporotic women as a group. The concentrations of 1,25(OH)₂D and 25(OH)D were significantly lower in patients with spinal fracture than in those with forearm fracture. In the early postmenopausal women, serum 1,25(OH)₂D was related to forearm bone mass (r=−0.20;P<0.05), intestinal calcium absorption (r=0.18;P<0.05), and 24-hour urinary calcium (r=0.21;P<0.05); serum 25(OH)D was related to spinal bone mass (r=0.23;P<0.01). In the osteoporotic women, serum vitamin D metabolites were not related to bone mass, but 1,25(OH)₂D was related to bone Gla protein (r=0.33;P<0.001), serum phosphate (r=−0.27;P<0.01), and 24-hour urinary calcium (r=0.43;P<0.001). The present study demonstrates that in a population that is apparently not deficient in vitamin D, a disturbance of the vitamin D metabolism is not likely to play a pathogenetic role in early postmenopausal bone loss. Patients with spinal fractures have low levels of vitamin D metabolites, which may aggravate their osteoporosis.     

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.     

Correlations between bone mineral density and demographic, lifestyle, and biochemical variables in community-dwelling Japanese women 69 years of age and over

Introduction A few epidemiologic studies have comprehensively attempted to identify risk factors for low bone mineral density (BMD) in elderly Asian women. The purpose of this study was to identify demographic, lifestyle, and biochemical factors correlated with BMD in elderly Japanese women 69 years of age and over.Methods The study design was cross-sectional. The subjects were 583 ambulatory women aged 69 years and over, and their average age was 74.3 (SD 4.4) years. Predictor variables were age, reproductive history, anthropometric indices, grip strength, calcium intake, lifestyle information, and serum 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D (1,25(OH)₂D), osteocalcin (OC), and undercarboxylated osteocalcin (ucOC) values. The outcome variable was forearm BMD measured with a DTX-200 osteometer.Results Simple linear regression analyses showed that BMD was significantly positively associated with body height, weight, body mass index, grip strength, serum albumin concentration, and “housework,” and negatively associated with age, years since menopause, age at menarche, number of children, serum 1,25(OH)₂D concentration, serum OC concentration, and ucOC concentration. The stepwise multiple regression analysis showed that weight (β=0.00316, SE=0.00028, R²=0.180), age (β=−0.00321, SE=0.00050, R²=0.108), log-transformed serum OC (β=−0.0445, SE=0.0064, R²=0.053), log-transformed serum 1,25(OH)₂D (β=−0.0401, SE=0.0074, R²=0.050), “farmwork” (β=0.00904, SE=0.00426, R²=0.005), and serum 25(OH)D concentration (β=0.000281, SE=0.000120, R²=0.003) were significantly associated with BMD.Conclusion It was concluded that body weight is a major predictor of forearm BMD among the factors measured in this study in independent Japanese women 69 years of age and over and that serum 1,25(OH)₂D concentration may be associated with cortical BMD. Maintenance of body weight is very important for maintaining BMD in this population, unless a large weight aggravates obesity-related diseases. A follow-up study is needed to confirm these findings.     

Effects of hPTH(1‐34) Infusion on Circulating Serum Phosphate, 1,25‐Dihydroxyvitamin D,and FGF23 Levels in Healthy Men

Fibroblast growth factor 23 (FGF23) promotes phosphaturia and suppresses 1,25‐dihydroxyvitamin D [1,25(OH)₂D] production. PTH also promotes phosphaturia, but, in contrast, stimulates 1,25(OH)₂D production. The relationship between FGF23 and PTH is unclear, and the acute effect of pharmacologically dosed PTH on FGF23 secretion is unknown. Twenty healthy men were infused with human PTH(1‐34) [hPTH(1‐34)] at 44 ng/kg/h for 24 h. Compared with baseline, FGF23, 1,25(OH)₂D, ionized calcium (iCa), and serum N‐telopeptide (NTX) increased significantly over the 18‐h hPTH(1‐34) infusion (p < 0.0001), whereas serum phosphate (PO₄) transiently increased and then returned to baseline. FGF23 increased from 35 ± 10 pg/ml at baseline to 53 ± 20 pg/ml at 18 h (p = 0.0002); 1,25(OH)₂D increased from 36 ± 16 pg/ml at baseline to 80 ± 33 pg/ml at 18 h (p < 0.0001); iCa increased from 1.23 ± 0.03 mM at baseline to 1.46 ± 0.05 mM at hour 18 (p < 0.0001); and NTX increased from 17 ± 4 nM BCE at baseline to 28 ± 8 nM BCE at peak (p < 0.0001). PO₄ was 3.3 ± 0.6 mg/dl at baseline, transiently rose to 3.7 ± 0.4 mg/dl at hour 6 (p = 0.016), and then returned to 3.4 ± 0.5 mg/dl at hour 12 (p = 0.651). hPTH(1‐34) infusion increases endogenous 1,25(OH)₂D and FGF23 within 18 h in healthy men. Whereas it is possible that the rise in PO₄ contributed to the observed increase in FGF23, the increase in 1,25(OH)₂D was more substantial and longer sustained than the change in serum phosphate. Given prior data that suggest that neither PTH nor calcium stimulate FGF23 secretion, these data support the assertion that 1,25(OH)₂D is a potent physiologic stimulator of FGF23 secretion.     

Comparison of metabolism of vitamins D2 and D3 in children with nutritional rickets

Children with calcium‐deficiency rickets may have increased vitamin D requirements and respond differently to vitamin D₂ and vitamin D₃. Our objective was to compare the metabolism of vitamins D₂ and D₃ in rachitic and control children. We administered an oral single dose of vitamin D₂ or D₃ of 1.25 mg to 49 Nigerian children—28 with active rickets and 21 healthy controls. The primary outcome measure was the incremental change in vitamin D metabolites. Baseline serum 25‐hydroxyvitamin D [25(OH)D] concentrations ranged from 7 to 24 and 15 to 34 ng/mL in rachitic and control children, respectively (p < .001), whereas baseline 1,25‐dihydroxyvitamin D [1,25(OH)₂D] values (mean ± SD) were 224 ± 72 and 121 ± 34 pg/mL, respectively (p < .001), and baseline 24,25‐dihydroxyvitamin D [24,25(OH)₂D] values were 1.13 ± 0.59 and 4.03 ± 1.33 ng/mL, respectively (p < .001). The peak increment in 25(OH)D was on day 3 and was similar with vitamins D₂ and D₃ in children with rickets (29 ± 17 and 25 ± 11 ng/mL, respectively) and in control children (33 ± 13 and 31 ± 16 ng/mL, respectively). 1,25(OH)₂D rose significantly (p < .001) and similarly (p = .18) on day 3 by 166 ± 80 and 209 ± 83 pg/mL after vitamin D₂ and D₃ administration, respectively, in children with rickets. By contrast, control children had no significant increase in 1,25(OH)₂D (19 ± 28 and 16 ± 38 pg/mL after vitamin D₂ and D₃ administration, respectively). We conclude that in the short term, vitamins D₂ and D₃ similarly increase serum 25(OH)D concentrations in rachitic and healthy children. A marked increase in 1,25(OH)₂D in response to vitamin D distinguishes children with putative dietary calcium‐deficiency rickets from healthy children, consistent with increased vitamin D requirements in children with calcium‐deficiency rickets. © 2010 American Society for Bone and Mineral Research     

Alteration in osteoblast activity and nutritional vitamin-D deficiency in non-hypercalcemic malignancy

Summary The biochemical parameters of bone mineral metabolism in patients with nonhypercalcemic malignancy have not been extensively investigated. Therefore, a group of 29 such patients with different types of malignancy was studied. Ten patients received corticosteroids. In the entire group, serum ionized calcium (Ca²⁺), bone gla protein (BGP), 25-hydroxyvitamin D (25OHD), and 1,25-dihydroxyvitamin D (1,25(OH)₂D) were all lower than in age-matched controls, and carboxy-terminal parathyroid hormone (CPTH) was higher. Although both corticosteroid- and noncorticosteroid-treated patients had decreased BGP values, the corticosteroid-treated patients had lower BGP levels than those not on steroids (4.24±0.70 SE vs. 11.50±2.20 ng/ml;P<0.005). Patients on corticosteroids had lower 1,25(OH)₂D values than controls (18.81 ±2.71 vs. 27.83±1.17 pg/ml;P<0.01), whereas those not on corticosteroids had normal 1,25(OH)₂D values. These results suggest that patients with nonhydpercalcemic malignancy have nutritional vitamin-D deficiency and secondary hyperparathyroidism with perhaps corticosteroid-induced suppression of serum 1,25(OH)₂D and BGP. The decreased levels of serum BGP in the nonsteroid-treated patients suggest, in addition, a defect in osteoblast function.     

Circulating β2 Microglobulin in Relation to Bone Metabolism: Implications for Bone Loss with Aging

The aim of this cross-sectional study was to evaluate the relationships between circulating β₂ microglobulin (β₂ m) and bone mineral density (BMD), parameters of bone remodeling, vitamin D metabolites, parathyroid hormone (PTH), estradiol levels, and age in a group of 165 clinically healthy or osteoporotic, but otherwise normal untreated women. In this group of women, systemic β₂ m correlated with BMD (g/cm²) levels for total hip and Ward's triangle (r =−0.298, P < 0.0001; and r =−0.299, P < 0.0001, respectively), but only at the borderline level with BMD at the spine (r =−0.145, P= 0.0604). Serum β₂ microglobulin markedly correlated with age (r = 0.512, P= 0.0001). β₂ m levels correlated with indices of bone remodeling, as well as with serum creatinine and estradiol levels. However, after stratification of all analyses by age, body mass index, and serum 25OHD₃, 1,25(OH)₂D₃, PTH, or estradiol levels (using standard multiple regression and stepwise forward regression models), only 25OHD₃ was found to be an independent predictor of BMD at the hip, including Ward's triangle, as estradiol of BMD at the spine. On the other hand, β₂ m was not associated with BMD at any of the measured regions. Also, no association was found between serum PTH and BMD values. Therefore, systemic β₂ m seems to be an indicator of bone remodeling in the course of natural skeletal aging rather than a variable independently predicting bone loss. Received: 21 July 1998 / Accepted: 10 June 1999