Decrease in bone level of 1,25-dihydroxyvitamin D in women over 45 years old

Summary The most active metabolite of vitamin D is 1,25-dihydroxyvitamin D [1,25(OH)₂D]. Its level in the bone may play a role in the pathogenesis of metabolic bone diseases such as osteoporosis. To assess this, and to see whether there is correlation between serum and bone levels, we studed serum and bone samples taken from 43 patients (18 men and 25 women) undergoing different orthopedic procedures. Patients were studied according to sex and age groups (<45 years, 46–60 years, >61 years). Serum level of 1,25(OH)₂D was found to be 29.7±2.61 pg/ml (mean±SEM) for women, 32.2±3.86 pg/ml for men, and 30.7±2.18 pg/ml for the group as a whole. No significant statistical differences were found among age subgroups in either sex or between sexes. Bone level of 1,25(OH)₂D was found to be 31.5±4.46 pg/g for women, 26.5±3.06 pg/g for men, and 29.4±2.81 pg/g for the entire group. No significant statistical difference was found between the age subgroups for men. However, the level of 1,25(OH)₂D was found to be higher in the group of younger women (<45 years) compared with the older women (46–60 years and >61 years) (P<0.005).Prof. T. Reichstein Professor of Biochemistry     

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.     

High Prevalence of Hypovitaminosis D among Free-Living Postmenopausal Women Referred to an Osteoporosis Outpatient Clinic in Northern Italy for Initial Screening

To establish the prevalence of hypovitaminosis D among free-living postmenopausal women referred to an osteoporosis outpatient clinic in Northern Italy, we evaluated 25-hydroxyvitamin D (25(OH)D) levels in 570 postmenopausal women who had been consecutively referred to our clinic in the 12 months beginning October 1995. Parathyroid hormone (PTH), serum calcium (Ca), creatinine (Cr) and osteocalcin (OC), urinary calcium (Ca24h) and creatinine (Cr24h), and the bone mineral density of the lumbar spine (LBMD) and femur (FBMD) were also measured. 1,25-Dihydroxyvitamin D (1,25(OH)₂D) concentrations were measured in 23 women. All women had normal electrolyte serum concentrations and kidney function. Mean ± SD 25(OH)D concentration was 18.3 ± 8.3 ng/ml. A significant (p<0.001) seasonal variation was seen for both 25(OH)D and PTH. Women were divided into two groups based on their vitamin D status: low vitamin D status (25(OH)D <12 ng/ml, n= 161, 28%) and normal vitamin D status (25(OH)D ≥12 ng/ml, n= 409, 72%). Hypovitaminosis D was found in 38.5% of all the women in the time period December–May and in 12.5% in the other half-year; among women >70 years old 51% had hypovitaminosis D in the time period December–May and 17% in the other half-year. PTH was significantly (p<0.05) increased, and Ca24h, OC and FBMD significantly (p<0.05) decreased in women with hypovitaminosis D. 1,25(OH)₂D positively correlated with 25(OH)D (p<0.0001), but did not correlate with PTH, age or creatinine clearance. In conclusion, hypovitaminosis D is an important, underestimated problem in Italian free-living postmenopausal women referred to an outpatient osteoporosis clinic. Received: 9 February 1998 / Accepted: 8 July 1998     

Metabolic effects of thiazide and 1,25-(OH)2 vitamin D in postmenopausal osteoporosis

It was previously shown that the stimulation of intestinal calcium absorption by exogenous 25-hydroxyvitamin D (25-OHD) in postmenopausal women with osteoporosis was attenuated when thiazide was added, probably due to the suppression of endogenous synthesis of 1,25-(OH)₂ vitamin D (1,25-(OH)₂D). To test whether the above attenuation could be averted if exogenous 1,25-(OH)₂D replaced 25-OHD, 10 women with postmenopausal osteoporosis participated in a three-phase study comprising control (pretreatment), treatment with 1,25-(OH)₂D 0.5 µg/day for 4 weeks, and combined 1,25-(OH)₂D and trichlormethiazide (TZ) 2 mg/day for 4 weeks. The 1,25-(OH)₂D treatment significantly increased serum 1,25-(OH)₂D from 60±7.2 (SD) to 154±48 pmol/1, fractional intestinal calcium absorption () from 0.386 ±0.055 to 0.613±0.081, and urinary calcium from 3.7±0.8 to 6.6±1.9 mmol/day. Addition of TZ significantly reduced urinary calcium from 6.6±1.9 to 4.8±1.3 mmol/day, without changing (0.613±0.081 to 0.584±0.070), serum calcium or 1,25-(OH)₂D (154±48 to 154±38 pmol/1). Thus, estimated calcium balance (absorbed minus urinary calcium, increased marginally to +5.6 mmol/day on 1,25-(OH)₂D alone (p=0.028) and significantly to +6.8 mmol/day on 1,25-(OH)₂D+TZ, from the control value of +4.0 mmol/day. Seven patients who were treated long-term with combined 1,25-(OH)₂D and TZ for 11–29 months maintained their a (0.593±0.099) and a marginally more positive estimated calcium balance (+6.4 mmol/day,p=0.025 from the control phase). Moreover, there was a stability of bone density of radial shaft, femoral neck, and lumbar spine. In conclusion, when exogenous 1,25-(OH)₂D is provided, TZ does not lower serum 1,25-(OH)₂D and in patients with postmenopausal osteoporosis. Thus, the hypocalciuric action of TZ may lead to improved calcium balance and may potentially attenuate further bone loss.     

Is there a differential response to alfacalcidol and vitamin D in the treatment of osteoporosis?

There is a decline in serum 25 hydroxyvitamin D (25OHD), 1,25 dihydroxyvitamin D (1,25(OH)₂D), and calcium absorption with advancing age, which may lead to secondary hyperparathyroidism and bone loss. Studies show a relationship between serum 25OHD and bone density in older men and women, with an inverse correlation between bone density and parathyroid hormone (PTH). Vitamin D supplementation in this age group improves calcium absorption, suppresses PTH, and decreases bone loss. Vitamin D many also reduce the incidence of hip and other nonvertebral fractures, particularly in the frail elderly who are likely to have vitamin D deficiency. Patients with established vertebral osteoporosis have lower calcium absorption than age-matched control subjects, possibly due to reduced serum 1,25(OH)₂D or to relative resistance to the action of vitamin D on the bowel. Malabsorption of calcium in women with vertebral crush fractures does not usually respond to treatment with physiological doses of vitamin D, but can be corrected by pharmacological doses of vitamin D or by low doses of calcitriol or alfacalcidol. In a recent randomized, controlled study in 46 elderly women with radiological evidence of vertebral osteoporosis, alfacalcidol 0.25 μg twice daily improved calcium absorption, decreased serum PTH, and reduced alkaline phosphatase, whereas vitamin D₂ 500–1000 IU daily had no effect over the 6-month study period. Studies of the effect of the vitamin D metabolites in the management of elderly women with established vertebral osteoporosis have yielded conflicting results, but suggest that alfacalcidol and calcitriol may decrease spinal bone loss and reduce the incidence of vertebral fractures. Although vitamin D supplementation decreases bone loss and fracture risk in the frail elderly, vitamin D metabolites may prove more useful in the treatment of elderly women with vertebral osteoporosis.     

Hormone replacement therapy increases serum 1,25-dihydroxyvitamin D: A 2-year prospective study

Osteoporosis is a common disorder in postmenopausal women, which is probably due to decreased ovarian function. Currently, hormone replacement therapy (HRT), involving administration of estrogen and progestogen, is successfully applied to reduce bone resorption. We studied the effect of HRT on 23 postmenopausal women. This consisted of a combination of 17-estradiol and dydrogesterone, on the serum level of 1,25-dihydroxyvitamin D (1,25(OH)₂D) after 0, 6, 12, and 24 months. We found mean serum concentrations (±SD) of 1,25(OH)₂D of 130.5 pmol/liter (46.1), 152.7 pmol/liter (45.1), 170.8 pmol/liter (64.0), and 155.2 pmol/liter (59.7), respectively. The baseline values in these women were found to be significantly lower than those during therapy (P0.005). No statistically significant differences were observed when comparing the estrogen-only phase with the combined estrogen-progestogen phase. It is concluded that HRT results in an increase in the serum 1,25(OH)₂D concentration which lasts for at least 2 years. This increase may partly explain the preventive effect of HRT on osteoporosis. Purthermore, these results suggest that dydrogesterone does not influence the estrogen-induced changes in serum 1,25(OH)₂D concentration.     

Decrease in bone levels of 1,25-dihydroxyvitamin D in women with subcapital fracture of the femur

Summary In a previous study we were able to show that in women over the age of 45 the level of 1,25-dihydroxyvitamin D (1,25(OH)₂D) in bone, but not in serum, is significantly reduced when compared with younger women. In the present study we measured the concentration of 1,25(OH)₂D in sera and bones of 19 female patients with subcapital fractures of the femur, mean age 78±2 years. We were able to show that serum levels of 1,25(OH)₂D were within the normal range, while bone levels were markedly reduced compared to levels in femoral bone obtained from young female cadavers or to the previously reported levels in non-osteoporotic elderly women. Thus, reduced levels of 1,25(OH)₂D in bones of elderly women may lead, together with other factors, to subcapital fractures.Holder of Prof. T. Reichstein Professorial Chair     

Reference database of biochemical markers of bone turnover for the Japanese female population. Japanese Population-based Osteoporosis (JPOS) Study

The present study was conducted as a part of the Japanese Population-based Osteoporosis (JPOS) Study to establish reference values on the biochemical markers of bone turnover in the general Japanese female population over an applicable age range. The study recruited 3250 women aged 15–79 years, randomly selected from five municipalities throughout Japan, and obtained measurements of serum osteocalcin (OC) and bone-specific alkaline phosphatase (BAP); free and total forms of immunoreactive deoxypyridinoline, free pyridinolines and type I collagen cross-linked C-terminal telopeptide (CTx) in urine; serum intact parathyroid hormone (PTH) and 1,25 dihydroxy vitamin D (1,25 (OH)₂D); and bone density at the spine, hip and distal forearm. After excluding subjects with apparent or suggested abnormalities affecting bone mass, 2535 (78%) subjects were further analyzed. The authors presented 5-year age-specific mean values of the markers and mean marker levels derived from women aged 30–44 years with normal bone density as a healthy young adult reference. Values of the markers decreased with increasing age before the age of 40, increased steeply among subjects in their 50s, and remained elevated in the elderly. Serum calcium, phosphorus, PTH and 1,25 (OH)₂D levels were higher in postmenopausal women than in premenopausal women. However, 1,25 (OH)₂D was lower among early postmenopausal subjects. The levels of OC, BAP, CTx, PTH and 1,25(OH)₂D were significantly greater for women with osteoporosis than for those without. The diagnostic value of the markers was limited as the sensitivity and specificity ranged from 55% to 60%. These findings will aid health professionals in the correct assessment of bone turnover status in Japanese women over a wide range of age.     

Vitamin D Therapy of Osteoporosis: Plain Vitamin D Therapy Versus Active Vitamin D Analog (D-Hormone) Therapy

Normal intestinal calcium (Ca) absorption is an essential feature of bone homeostasis. As with many other organ systems, intestinal Ca absorption declines with aging, and this is one pathological factor that has been identified as a cause of senile osteoporosis in the elderly. This abnormality leads to secondary hyperparathyroidism, which is characterized by high serum parathyroid hormone (PTH) and an increase in bone resorption. Secondary hyperparathyroidism due to poor intestinal Ca absorption has been implicated not only in senile osteoporosis but also in age-related bone loss. Accordingly, in population-based studies, there is a gradual increase in serum PTH from about 20 years of age onward, which constitutes a maximum increase at 80 years of age of 50% of the basal value seen at 30 years of age. The cause of the increase in PTH is thought to be partly due to impaired intestinal Ca absorption that is associated with aging, a cause that is not entirely clear but at least in some instances is related to some form of vitamin D deficiency. There are three types of vitamin D deficiency: (1) primary vitamin D deficiency, which is due to a deficiency of vitamin D, the parent compound; (2) a deficiency of 1,25(OH)₂D₃ resulting from decreased renal production of 1,25(OH)₂D₃; and (3) resistance to 1,25(OH)₂D₃ action owing to decreased responsiveness to 1,25(OH)₂D₃ of target tissues. The cause for the resistance to 1,25(OH)₂D₃ could be related to the finding that the vitamin D receptor level in the intestine tends to decrease with age. All three types of deficiencies can occur with aging, and each has been implicated as a potential cause of intestinal Ca malabsorption, secondary hyperparathyroidism, and senile osteoporosis. There are two forms of vitamin D replacement therapies: plain vitamin D therapy and active vitamin D analog (or D-hormone) therapy. Primary vitamin D deficiency can be corrected by vitamin supplements of 1000 U a day of plain vitamin D whereas 1,25(OH)₂D₃ deficiency/resistance requires active vitamin D analog therapy [1,25(OH)₂D₃ or 1α(OH)D₃] to correct the high serum PTH and the Ca malabsorption. In addition, in the elderly, there are patients with decreased intestinal Ca absorption but with apparently normal vitamin D metabolism. Although the cause of poor intestinal Ca absorption in these patients is unclear, these patients, as well as all other patients with secondary hyperparathyroidism (not due to decreased renal function), show a decrease in serum PTH and an increase in Ca absorption in response to therapy with 1,25(OH)₂D₃ or 1α(OH)D₃. In short, it is clear that some form of vitamin D therapy, either plain vitamin D or 1,25(OH)₂D₃ or 1α(OH)D₃, can be used to correct all types of age-dependent impairments in intestinal Ca absorption and secondary hyperparathyroidism during aging. However, from a clinical standpoint, it is important to recognize the type of vitamin D deficiency in patients with senile osteoporosis so that primary vitamin D deficiency can be appropriately treated with plain vitamin D therapy, whereas 1,25(OH)₂D₃ deficiency/resistance will be properly treated with 1,25(OH)₂D₃ or 1α(OH)D₃ therapy. With respect to postmenopausal osteoporosis, there is strong evidence that active vitamin D analogs (but not plain vitamin D) may have bone-sparing actions. However, these effects appear to be results of their pharmacologic actions on bone formation and resorption rather than through replenishing a deficiency.     

Effect of a long-term treatment with 1,25-dihydroxyvitamin D3 on osteocalcin in postmenopausal osteoporosis

Summary Serum bone Gla-protein (BGP or osteocalcin) was measured in 25 women with histologically confirmed postmenopausal osteoporosis before and during long-term treatment with 1 μg/day of 1,25-dihydroxyvitamin D₃(1,25(OH)₂D₃). Basal serum BGP was significantly lower in osteoporotic women (3.8±1.4 ng/ml) than in agematched controls (6.8±2.0 ng/ml). During 1,25(OH)₂D₃ therapy serum BGP increased so that the mean of the values observed on treatment (4.8±1.5) was significantly higher than the mean basal value. It is known that BGP synthesis is stimulated by 1,25 (OH)₂D₃ and that serum BGP is a specific marker of bone formation; therefore, it is possible that the low basal levels of osteocalcin we observed were related to the low serum 1,25(OH)₂D concentrations reported in osteoporotic women and that the increase in BGP levels observed under 1,25(OH)₂D₃ treatment was a consequence of osteoblast stimulation.     

Relationship Between Disease Activity and Serum Levels of Vitamin D Metabolites and PTH in Rheumatoid Arthritis

In several studies on patients with rheumatoid arthritis, an association of bone loss with a persistently high disease activity has been found. The aim of our study was to investigate the relation between disease activity and serum levels of vitamin D metabolites, parathyroid hormone (PTH), and parameters of bone turnover in patients with rheumatoid arthritis. A total of 96 patients (83 women and 13 men) were divided into three groups according to disease activity measured by serum levels of C-reactive protein (CRP). In the whole group, serum levels of 1,25-dihydroxyvitamin D3 (1,25(OH)₂D₃) (P < 0.001) and PTH (P < 0.05) were negatively correlated to disease activity. The urinary excretion of collagen crosslinks—pyridinoline (Pyd) (P < 0.001) and deoxypyridinoline (Dpd) (P < 0.05)—showed a positive correlation with disease activity. The inverse correlation between serum 1,25(OH)₂D₃ and disease activity was separately evident in patients with (P < 0.001) and without (P < 0.01) glucocorticoid treatment, in pre- (P < 0.01) and postmenopausal (P < 0.001) women, and in men (P < 0.01). 1,25(OH)₂D₃ and PTH serum levels were positively correlated to serum bone alkaline phosphatase (ALP) (P < 0.01). The results indicate that high disease activity in patients with rheumatoid arthritis is associated with an alteration in vitamin D metabolism and increased bone resorption. The decrease of 1,25(OH)₂D₃ levels in these patients may contribute to a negative calcium balance and inhibition of bone formation. Furthermore, low levels of 1,25(OH)₂D₃ as an endogenous immunomodulator suppressing activated T cells and the proliferation of cells may accelerate the arthritic process in rheumatoid arthritis. Received: 3 February 1997 / Accepted: 26 June 1997     

Malabsorption of calcium in corticosteroid-induced osteoporosis

Summary We have examined the relation between radiocalcium absorption and serum 1,25-dihydroxy-vitamin D [1,25(OH)₂D₃] levels in a set of 60 postmenopausal women on corticosteroid therapy (29 with and 31 without vertebral compression fractures) and compared these results with those from 31 normal postmenopausal women age-matched with the “normal” corticosteroid-treated women. Radiocalcium absorption was a function of serum 1,25(OH)₂D₃ in both corticosteroid-treated groups and in the set as a whole, but the impaired calcium absorption in the corticosteroid-treated patients with osteoporosis was not accounted for by their slightly reduced serum 1,25(OH)₂D₃ levels. This apparent resistance to the intestinal action of 1,25(OH)₂D₃ was quantified by a Z score which expresses, in standard deviation units, the difference between the measured calcium absorption and that predicted from the 1,25(OH)₂D₃ level. The Z score was significantly reduced in the osteoporotic group. Vertebral mineral density (VMD) was measured by quantitative computed tomography in 43 of the corticosteroid-treated cases and in all the normal postmenopausal women; analysis by VMD yielded similar conclusions.     

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.     

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.     

Short-term course of 1,25(OH)2D3 stimulates osteoblasts but not osteoclasts in osteoporosis and osteoarthritis

Summary We investigated the effect of short-term, 1,25-dihydroxyvitamin D₃ therapy (4 μg/day for 4 days) on calcium metabolism in 27 postmenopausal women (11 cases with osteoporosis and 16 cases with osteoarthritis). Bone mass at the axial and appendicular skeleton was higher in osteoarthritis than in osteoporosis. Initial values of calcium metabolism were similar. Osteoporotic and osteoarthritic patients responded with a similar significant increase in serum osteocalcin (+61% and +54%, respectively), fasting urinary calcium excretion (+178% and +124%, respectively) and 24 hour calcium excretion (+148% and +142%, respectively). Parathyroid hormone (PTH) levels decreased significantly in both groups (−30% and −18%, respectively). Osteoclastic bone resorption, evaluated by urinary hydroxyproline excretion, was not stimulated in either group. We conclude that in osteoporosis and also in osteoarthritis (1) 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃) stimulation of osteoblast function is similar in production of osteocalcin; (2) the vitamin D target tissues react adequately to 1,25(OH)₂D₃ stimulation; (3) short-term high dose of 1,25(OH)₂D₃ does not stimulate bone resorption; and (4) the differences in bone mass between osteoarthritis and osteoporosis are not related to an alteration of the responsiveness to stimulation by 1,25 (OH)₂D₃.     

Biochemical Responses of Bone Metabolism to 1,25-Dihydroxyvitamin D Administration in Black and White Women

The basis for the racial difference in bone mass between black and white women is not known. Lower bone turnover, better renal calcium conservation, and decreased sensitivity to parathyroid hormone (PTH) have been proposed as explanations. A dynamic comparison of osteoblast function, utilizing stimulation by 1,25-dihydroxyvitamin D [1,25(OH)₂D], has not been tested between these two ethnic groups. We compared well-matched black (n= 15) and white (n= 15) premenopausal women, before and during 5 days of 1,25(OH)₂D administration (1.0 μg/day) in order to assess dynamic indices of bone metabolism. As expected, at baseline, black women had lower levels of serum 25-hydroxyvitamin D and biochemical markers of bone turnover with slightly higher levels of PTH. Black women also had superior renal calcium conservation than white women at baseline. In response to 1,25(OH)₂D administration, black women had a slightly greater increase in serum calcium and greater decrement in PTH. Moreover, black women showed a lesser increment in urinary calcium than white women and a more robust increase in two markers of bone formation – osteocalcin and carboxyterminal propeptide of type 1 procollagen – than white women. There were no changes in bone resorption indices in either race upon 1,25(OH)₂D administration. These data provide preliminary evidence that black women conserve calcium more efficiently under both static and dynamic conditions, and also appear to have better osteoblastic functional reserve than white women. Received: 22 June 1999 / Accepted: 6 September 1999     

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.     

Tumoral calcinosis: Evidence for concurrent defects in renal tubular phosphorus transport and in 1α,25-dihydroxycholecalciferol synthesis

Summary A 50-year-old Latin American man with tumoral calcinosis presented with hyperphosphatemia (6.62±1.04 SD mg/dl), elevated renal threshold phosphorus concentration (TmP) (7.3 mg/GFR), and 1,25-dihydroxyvitamin D [1,25-(OH)₂D] (69 pg/ml) hypercalciuria (239 mg/day), and a high fractional intestinal calcium (Ca) absorption (0.74). Sodium cellulose phosphate therapy (20 g/day) lowered urinary Ca, and partially reduced serum phosphorus (P) and TmP to 5.91±0.63 mg/dl and 6.2 mg/GFR, respectively. Serum 1,25-(OH)120D remained elevated at 58–64 pg/ml. Amphojel therapy (4 oz/day) decreased urinary P to 23±21 mg/day and lowered serum P to 5.75±0.36 mg/dl (P<0.05). TmP increased to a value of 8.0 mg/GFR while serum 1,25-(OH)₂D continued to remain elevated at 53 pg/ml. This case illustrates the probable operation of dual abnormalities in tumoral calcinosis represented by augmented renal conservation of P and an elevation in the circulating concentration of 1,25-(OH)₂D.     

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.     

Vitamin D metabolites in childhood nephrotic syndrome

We measured serum levels of total and ionised calcium, phosphate, intact parathyroid hormone, 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)₂D] and the vitamin D binding protein (DBP) in 14 children with idiopathic nephrotic syndrome and 10 healthy, age-matched controls. In all nephrotics serum DBP levels were below the normal range. Serum 25(OH)D was below 7 ng/ml in 10 of 14 nephrotic children and in the low normal range in the remaining 4 patients. The average serum 1,25(OH)₂D levels were lower in the nephrotic patients than in the controls. However, free 1,25(OH)₂D levels were normal in the nephrotic patients. Both serum 25(OH)D and 1,25(OH)₂D correlated positively with the concentration of DBP There was a significant negative correlation between serum DBP levels and the urinary protein excretion and a significant positive correlation between the urinary excretions of DBP and albumin. From this study it can be concluded that the nephrotic child is capable of maintaining appropriate serum concentrations of free calcitriol despite important urinary losses of both substrate and bound calcitriol.