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.     

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.     

Treatment of hyperparathyroidism with cinacalcet in kidney transplant recipients

Background

After successful kidney transplantation, hyperparathyroidism can persist in 10%–50% of patients and can harmfully affect bone metabolism. Calcimimetic cinacalcet is a new treatment option in the management of persistent hyperparathyroidism in these patients.

Methods

This prospective, clinical study of 11 patients included those who had a serum intact parathyroid hormone (iPTH) concentration >65 ng/L, a serum creatinine concentration was <200 μmol/L, stable kidney graft function, and were >1 year since transplantation. Patients were not treated with drugs other than calcitriol that could influence bone metabolism. During the 6-month observation period, in which the stability of measured parameters was determined, and in the 12-month treatment period (cinacalcet 30 mg/d), we followed serum concentrations of calcium, phosphate, iPTH, creatinine, vitamin 25OH D₃, bone-specific alkaline phosphatase (ALP), osteocalcin, collagen degradation fragments (CTX), urinary calcium excretion, and bone mineral density (BMD).

Results

During the treatment period, the serum calcium concentration decreased significantly (from 2.50 ± 0.12 to 2.32 ± 0.12 mmol/L; P < .01). Serum iPTH concentration decreased significantly (from 247 [range, 199–362] at time 0 to 198 [range, 165–233] ng/L after 1 month of treatment; P < .05), but increased slightly thereafter. After 6 months of treatment, the serum concentration of ALP and CTX increased significantly, but decreased thereafter. There were no significant changes in the other parameters assessed. Renal function remained stable during the treatment period. The BMD of the lumbar spine, hip, and forearm did not change during the 12 months of treatment.

Conclusion

Cinacalcet was effective in treating posttransplant hyperparathyroidism, resulting in decreased calcemia and transient decreased iPTH. ALP and CTX transiently increased during therapy, but other markers of bone metabolism remained unchanged. Twelve months of cinacalcet treatment did not result in a change in BMD. Cinacalcet seems to be a safe drug with no negative effect on renal function.     

Disordered mineral metabolism produced by ketogenic diet therapy

Summary Vitamin D and mineral metabolism status was examined in five children maintained chronically on combined ketogenic diet-anticonvulsant drug therapy (KG), and the results compared to those obtained in 18 patients treated with anticonvulsant drugs alone (AD) and 15 normal controls. KG patients exhibited biochemical findings of vitamin D deficiency osteomalacia: decreased serum 25-hydroxyvitamin D (25OHD) and calcium concentrations, elevated serum alkaline phosphatase and parathyroid hormone concentrations, decreased urinary calcium and increased urinary hydroxyproline excretion, and decreased bone mass. Although the KG and AD groups demonstrated similar reductions in serum 25OHD concentration, the KG patients exhibited a significantly greater reduction in bone mass. In response to vitamin D supplementation (5000 IU/day), mean bone mass in the KG group increased by 8.1±0.9% (P<0.001) over a 12-month period. These results suggest that ketogenic diet and anticonvulsant drug therapy have additive deleterious effects on bone mass and that these effects are partially reversible by vitamin D treatment.     

Different actions of vitamin D2 and D3 on bone metabolism in patients treated with phenobarbitone/phenytoin

Summary In 22 epileptic outpatients treated for at least 1 year with phenobarbitone/phenytoin the local and total bone mass, together with serum and urinary indices of calcium metabolism, were measured before and during treatment with either vitamin D₂ or D₃, 4,000 IU daily for 24 weeks. The results showed a distinct difference in the action of the two vitamins on bone metabolism during anticonvulsant treatment. The bone mass increased during treatment with vitamin D₂, whereas the vitamin D₃-treated patients showed unchanged values of bone mass, but an increased excretion rate of calcium, probably caused by increased intestinal calcium absorption. The data demonstrate that vitamins D₂ and D₃ (or their metabolites) have quantitative different effects in patients treated with phenobarbitone/phenytoin.     

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.     

Does 24R,25(OH)2-vitamin D3 prevent postmenopausal bone loss?

Summary The effect of oral 24R,25(OH)₂-vitamin D₃ as a prophylactic for postmenopausal bone loss was examined. Fifty-eight healthy, early postmeno-pausal women entered a double blind therapeutic trial for 2 years. After an initial examination the women were randomized to treatment with 10 μg 24R,25(OH)₂D₃ daily or placebo. Participants were thereafter examined every 3 months (nine examinations in all). In both groups the forearm bone mineral (measured by single photon absorptiometry), the lumbar spine mineral, and the total body mineral (measured by dual photon absorptiometry) fell significantly and the same magnitude. Further-more, serum calcium, serum alkaline phosphatase concentration, and fasting urinary hydroxyproline were unchanged, as were the 24-hour urinary calcium excretion and the intestinal radiocalcium absorption. Our findings demonstrate that 24R,25(OH)₂D₃ treatment has no prophylactic effect on postmenopausal bone loss and does not alter calcium metabolic variables.     

Immobility as a Major Cause of Bone Remodeling in Residents of a Long-Stay Geriatric Ward

Residents of a long-stay geriatric ward at the University Hospital Basel were included in a study to investigate the effects of hypovitaminosis D and immobility. All 91 women (mean age 82.5 years) and 92 men (mean age 78.7 years) were enrolled in the study. Measurements included bone resorption, as measured by urinary deoxypyridinoline (dpd), serum 25-hydroxyvitamin D (25OHD), serum intact parathyroid hormone (iPTH), and their correlations with a four grade mobility score. Mobility score reflected the degree of weight bearing, ranging from walking independently to primarily bed bound. In 86% of all residents, serum 25OHD levels were below the normal limit of 12 ng/ml. Secondary hyperparathyroidism (HPT) was detected in 24% of all patients, using 55 pg/ml as the upper limit for serum iPTH. No significant correlation was found between urinary dpd and serum 25OHD or serum iPTH. Mobility index and both urinary dpd (f: P= 0.001, r = 0.37; m: P < 0.0001, r= 0.47) and serum calcium (female: P= 0.007, r = 0.28; male: P= 0.02, r= 0.24) were positively related. In institutionalized elderly people with a high prevalence of vitamin D deficiency serum intact PTH levels did not correlate with bone resorption as measured by urinary deoxypyridinolin. However, more immobile subjects had significantly higher excretion rates for urinary dpd and higher serum calcium levels. Our results suggest that in elderly people immobility may contribute to bone loss that might preempt the development of secondary HPT through elevation of serum calcium. Received: 12 February 1998 / Accepted: 1 November 1998     

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     

Calcium absorption measurements in normal subjects in determining calcium deposition during prolonged hypokinesia and with and without calcium loading

Measuring calcium (Ca) absorption, Ca balance and Ca level in serum,feces and urine during HK (hypokinesia) with and without Ca loading, the aim of this study was to disclose if prolonged HK could reduce Ca deposition more with or without Ca load contributing to greater Ca imbalance. Studies were conducted during 30-days pre-HK and 364-days HK. Forty male normal volunteers 23.7 ± 6.0 years of age were chosen as subjects. They were divided into four groups: unloaded active control subjects (UACS), unloaded hypokinetic subjects (UHKS), loaded active control subjects (LACS), loaded hypokinetic subjects (LHKS). All hypokinetic subjects were walking average distances of 0.5 ± 0.2 km day^–1, and active control subjects were running average distances of 6.6 ± 1.2 km day^–1. LACS and LHKS were loaded with 1.3 mmol calcium lactate/kg body wt. Before Ca load, fecal Ca loss, urinary Ca and phosphate (P) losses, Ca imbalance, serum ionized calcium (Ca_I), P and total Ca (Ca_t) levels increased significantly. (P < 0.05) with time, and serum intact parathyroid hormone (iPTH), 1.25 dihydroxyvitamin D (1.25(OH)₂D₃) levels and Ca absorption, decreased significantly (P < 0.05) with time in LHKS and UHKS compared with their pre-HK values and their respective active controls (LACS and UACS). After Ca load, however, Ca absorption, serum iPTH and 1.25 (OH)₂D₃ levels decreased significantly (P < 0.05) more with time, while fecal Ca loss, urinary Ca and P excretion and Ca imbalance increased significantly (P < 0.05) more with time in LHKS than UHKS. Conversely, before and after Ca load, fecal Ca excretion, urinary P and Ca loss, serum Ca_I, P, Ca, iPTH and 1.25 (OH)₂D₃ levels, Ca absorption and Ca balance did not change in LACS and UACS compared with their pre-HK values. The greater Ca losses with than without Ca load have shown that the more Ca is consumed the more Ca is eliminated during HK and Ca imbalance. The significant increase of Ca loss with Ca imbalance demonstrated reduced Ca deposition. Dissociation between Ca loss and Ca imbalance demonstrated reduced Ca deposition as the mechanism of Ca imbalance development during HK.     

Effects of parathyroidectomy on bone remodeling markers and vitamin D status in patients with chronic kidney disease–mineral and bone disorder

Background/Aims Chronic renal failure (CRF) is often associated with bone disorders including chronic kidney disease–mineral and bone disorder (CKD–MBD). Parathyroid hormone (PTH) has a relationship to bone remodeling, and so this study was undertaken to evaluate changes in bone remodeling markers after parathyroidectomy (PTX). Methods Twelve adult patients, mean age 43.4 ± 12.7 years, of both genders, were evaluated, prior to and six months after PTX. Analysis of biochemical markers of bone metabolism, such as total and ionized calcium, phosphorus, 25(OH)D₃, total alkaline phosphatase (TAP), bone-specific alkaline phosphatase (BAP), intact PTH, osteoprotegerin (OPG), and tartrate-resistant acid phosphatase isoform 5b (TRAP), were measured. Results No changes were observed after PTX in the serum total and ionized calcium, TAP, BAP, and 25(OH)D₃. After surgery there was a significant decrease in serum phosphorus, iPTH, and TRAP (P < 0.001). No significant change was observed in OPG; however there was a positive correlation between OPG and 25(OH)D₃ before and after surgery (r = 0.774, P = 0.014; and r = 0.706, P = 0.01, respectively). The percentage of patients with vitamin D deficiency decreased from 16.7% to 8.3%, while those with sufficient levels increased from 41.7% to 58.3%. Conclusion The small number of patients in the study notwithstanding, the present study is unique because it provides information on bone metabolism and vitamin D status six months after PTX. The removal of parathyroid glands significantly decreased bone resorption and indicated a tendency of 25(OH)D₃ concentration to increase. However, the precise role of OPG and BAP in the improvement in bone remodeling in patients with CKD–MBD requires further study.     

Seasonal variation in bone metabolism in young healthy subjects

Summary Serum vitamin D metabolites and urinary calcium excretion; parameters of bone formation (serum alkaline phosphatase, serum osteocalcin); parameters of bone resorption (24 hour hydroxyprolinuria, 2 hour fasting urinary hydroxyproline/creatinine ratio); and parameters of cortical and trabecular bone density, parathyroid hormone (iPTH, COOH terminal assay), and serum minerals (calcium, phosphorus) were followed serially in 55 young adults (21 women and 34 men) from December 1985 until January 1987 at four different times during the year. The effect of a low-dose cyclooxygenase inhibitor (piroxicam 5 mg daily) on the same parameters of bone density and bone turnover when given from December until May, was also evaluated in this study. At the end of the treatment period parameters of bone turnover and bone density were comparable between placebo and piroxicam-treated groups. Therefore, the results of all subjects were pooled in order to investigate seasonal variation. In both sexes, seasonal variation was found not only for 250HD₃ but also for 1,25(OH)₂D₃, serum calcium and phosphorus, urinary calcium excretion, and for bone density at the lumbar spine. Parameters of bone formation (serum osteocalcin and alkaline phosphatase), bone resorption (24 hour urinary hydroxyprolinuria and fasting urinary hydroxyproline/creatinine ratio) and PTH were influenced by this seasonal variation. We conclude that in young adults, a significant seasonal variation occurs, with low winter and high summer values, for serum 25 and 1,25(OH)₂D₃ for urinary calcium apparently without important influence on parameters of bone turnover or parathyroid activity and for lumbar spine density. Treatment with a low-dose cyclooxygenase inhibitor was without influence on the observed changes.     

Serum vitamin D metabolites are not related to growth rate,bone mineral content,or serum alkaline phosphatase in male puberty

Summary Twenty boys were followed during their puberty for about 2 years with examinations every third month. At each examination we determined serum concentrations of 25OHD₃, 1,25(OH)₂D₃, 24,25(OH)₂D₃, 25.26(OH)₂D₃,alkaline phosphatase (AP) and testosterone together with bone mineral content (BMC) at the distal forearm. Highly significant increases in both BMC (P<0.001), serum AP (P<0.001), and peak height velocity (PHV) followed the increase in serum testosterone. The boys were grouped according to time of maximal increase in BMC, AP, and PHV. The serum levels of the vitamin D metabolites were related to these points. No significant changes in any of the serum vitamin D metabolites were found. Thus vitamin D metabolism does not seem to be significantly influenced during the period of life when both the linear growth and bone mineralization is maximal.     

Prednisolone Induces an Increase in Serum Calcium Concentration: Possible Involvement of the Kidney, the Bone, and the Intestine

To evaluate the early effect of glucocorticoids on calcium metabolism, 15 subjects aged 22–58 years (5 males, 10 females) with chronic glomerulonephritis were orally treated with 40 mg daily of prednisolone. Five of these subjects were diagnosed with nephrotic syndrome and none had a serum creatinine concentration of more than 1.4 mg/dl. Serum specimens and 24-hour urine specimens were obtained just before and 24 hours after a single oral dose of prednisolone. Serum calcium, ionized calcium, phosphate, intact parathyroid hormone (PTH), intact osteocalcin and 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃), and urinary excretion of calcium, phosphate, and deoxypyridinoline were measured. Both serum calcium and ionized calcium concentrations were significantly increased from 4.39 ± 0.10 to 4.47 ± 0.09 mEq/liter (P= 0.037) and from 2.48 ± 0.04 to 2.55 ± 0.04 mEq/liter (P= 0.002), respectively, 24 hours following a single oral dose of prednisolone. Serum intact PTH concentration slightly decreased, but the difference was not significant by statistical analysis. Serum intact osteocalcin concentration was markedly suppressed. In contrast, no significant changes were observed in urinary excretion of deoxypyridinoline. Serum 1,25(OH)₂D₃ concentration measured in five patients was significantly increased. No significant changes in urinary excretion of calcium was observed in the face of these findings. It thus follows that a single oral dose of prednisolone administration increases serum calcium and ionized calcium concentrations, possibly mediated by suppressed bone formation, increased intestinal absorption of calcium, and impaired urinary excretion of calcium. Received: 19 February 1998 / Accepted: 12 March 1999     

Calcium,vitamin D-endocrine system,and parathyroid hormone in black and white males

Summary The serum and urinary calcium, 25-hydroxyvitamin D (25OHD), 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃), and parathyroid hormone (PTH) were studied in healthy black and white males living in Belgium, and the results were compared to data in blacks of similar age living in Za?re. Dietary calcium and vitamin D were estimated in a subsample of blacks and whites examined in Belgium. Compared to whites (9.51±0.28 mg%) serum calcium was somewhat lower in blacks (9.26±0.27 mg% in Belgium; 9.19±0.48 mg% in Za?re). The 24 hour urinary calcium excretion averaged 215.0±16.7 mg% in whites and was higher (P<0.05 or less) than in blacks (115±71 mg% in Belgium; 36±33 mg% in Za?re). The serum 25OHD levels were similar in whites and blacks evaluated in Za?re, both being higher (P<0.05 or less) than in blacks living in Belgium. In the latter blacks, an inverse correlation was observed between the 25OHD level and the duration of the stay in a temperate climate. Parathyroid hormone levels were slightly higher in blacks living in Belgium than in the other two groups of subjects. The serum levels of 1,25(OH)₂D₃ and human vitamin D-binding protein were similar in the three groups of subjects. Dietary calcium averaged 541±152 mg/day in blacks and was significantly (P<0.001) less than in whites (1,203±508 mg/day), whereas no significant difference was observed in dietary vitamin D intake between blacks and whites. It is concluded that calcium intake is low in blacks but stimulation of parathyroid hormone and 1,25(OH)₂D₃ required to achieve normocalcemia does not occur.     

Action of vitamin D metabolites on PTH secretion in man

Summary We have examined the effects of metabolites of vitamin D [25OHD₃, 1,25(OH)₂D₃, 24,25(OH)₂D₃, and 25,26(OH)₂D₃] on serum calcium and iPTH in human deficient-D osteomalacia. The four metabolites decreased iPTH, but only for 1,25(OH)₂D₃ was a significant correlation between increase of serum calcium and decrease of iPTH observed. The 24,25(OH)₂D₃ and 25,26(OH)₂D₃ decreased iPTH despite a decrease of serum calcium at the beginning of treatment. The 25OHD decreased iPTH before increased serum calcium. These results could be interpreted as a direct effect of metabolites of vitamin D on PTH secretion. However, the conversion of other metabolites and the calcium concentration in parathyroid cells must be determined before this hypothesis can be accepted.     

Recovery of Bone Mineral Density in 126 Patients after Surgery for Primary Hyperparathyroidism

Primary hyperparathyroidism (pHPT) is associated with increased fracture risk and decreased bone mass. The recovery of bone mass after surgery varies; therefore tests that predict the increase in bone mass after parathyroidectomy would be desirable. Preoperatively and at 1 year after surgery bone mineral content (BMC) in the distal radius and bone mineral density (BMD) in the lumbar spine and hip, as well as biochemical variables, were measured in 126 pHPT patients (95 women, 31 men). The mean ± SD age of the patients was 63 ± 15 years. The mean ± SD serum calcium level was 2.78 ± 0.16 mmol/L. Altogether, 60% of the patients had a low oral calcium intake, and 18% had a 25-hydroxyvitamin D₃ deficiency. Preoperatively, postmenopausal women had lower Z-scores for BMD in the hip (p < 0.001) and lumbar spine (p < 0.05) than did premenopausal women. One year after surgery the bone density had increased in about 50% of the patients. The multiple logistic regression analysis showed that there was a weak association between the change in BMD in the hip, the serum 1,25-dihydroxyvitamin D₃ level (p < 0.05), and renal function (p < 0.05), respectively. We concluded that about 50% of patients have increased bone mass after pHPT surgery, but the increase in the bone density is difficult to predict for the individual patient. Because many pHPT patients have low oral calcium intake and a vitamin D deficiency, it would be of interest to evaluate the role of postoperative calcium/vitamin D supplements.     

Serum bone gla protein (BGP) and other markers of bone mineral metabolism in postmenopausal osteoporosis

Summary Bone gla protein, the vitamin K-dependent protein synthesized by osteoblasts and measured in blood by radioimmunoassay, has been used as an index of the rate of bone turnover. The relationship of bone gla protein with other markers of bone mineral metabolism was determined in 31 untreated postmenopausal women with the osteoporotic syndrome. In addition to serum osteocalcin (BGP) we measured parathyroid hormone (PTH) (carboxyl and mid-molecule fragments), 25(OH)D, alkaline phosphatase, estradiol (E₂), estrone (E₁), dietary calcium intake, 24 hour urinary calcium excretion, and bone mineral density by CT scan of the lumbar vertebrae. Significant osteopenia was present on CT in untreated postmenopausal osteoporotic women (bone density in 18 out of 31 was below the critical value of 60 mg/cm³). Serum BGP correlated positively with CT scan (r+0.647,P<0.001). CT and age were negatively correlated (r−0.661,P<0.001) while CT and E₂ showed a positive correlation (r+0.554,P<0.01). Unexpectedly, BGP and age revealed a significant negative correlation (r−0.421,P<0.05). These findings suggest a state of low bone turnover in this group with untreated postmenopausal osteoporosis.     

Calcium and Vitamin D Supplementation Increases Spinal BMD in Healthy, Postmenopausal Women

We undertook a double-masked, randomized, placebo-controlled trial to evaluate the effect of a calcium and vitamin D supplement and a calcium supplement plus multivitamins on bone loss at the hip, spine and forearm. The study was performed in 240 healthy women, 58–67 years of age. Duration of treatment was 2 years. Bone mineral density (BMD) was measured at the lumbar spine, hip and forearm. A dietary questionnaire was administered twice during the study and revealed a fairly good calcium and vitamin D intake (919 mg calcium/day; 3.8 mg vitamin D/day). An increase in lumbar spine BMD of 1.6% was observed in the treatment group after 2 years (p50.002). In the placebo group no significant changes were observed during the 2 years. Lumbar spine BMD was significantly higher in the treatment group at both 1 (p50.01) and 2 years (p50.05) compared with the placebo group. Though not significant, the same trend was seen at the hip. No significant changes from baseline values were observed at the distal forearm in either the treatment or the placebo group. In conclusion, we found a significant increase in urinary calcium excretion in the treatment group compared with the placebo group. Together with significant changes in serum calcium and serum parathyroid hormone, this indicates that a long-term calcium and vitamin supplement of 1 g elementary calcium (calcium carbonate) and 14 mg vitamin D₃ increases intestinal calcium absorption. A positive effect on BMD was demonstrated, even in a group of early postmenopausal age, with a fairly good initial calcium and vitamin D status. Received: 2 July 1997 / Accepted: 28 October 1997