Serum parathyroid hormone is associated with increased cortical porosity of the inner transitional zone at the proximal femur in postmenopausal women: the Tromsø Study.

Serum parathyroid hormone (PTH) was associated with increased bone turnover markers and cortical porosity of the inner transitional zone at the proximal femur. These results suggest that PTH through increased intracortical bone turnover leads to trabecularisation of inner cortical bone in postmenopausal women. INTRODUCTION: Vitamin D deficiency leads to secondary hyperparathyroidism and increased risk for fractures, whereas its association with cortical porosity is less clear. We tested (i) whether serum 25-hydroxyvitamin D (25(OH)D) and PTH were associated with cortical porosity and (ii) whether the associations of 25(OH)D) and PTH with fracture risk are dependent on cortical porosity. METHODS: This case-control study included 211 postmenopausal women, 54-94 years old, with prevalent fractures and 232 controls from the Tromsø Study. Serum 25(OH)D, PTH, and bone turnover markers (procollagen type I N-terminal propeptide [PINP] and C-terminal cross-linking telopeptide of type I collagen [CTX]) were measured. Femoral subtrochanteric cortical and trabecular parameters were quantified using computed tomography, and femoral neck areal bone mineral density (FN aBMD) was quantified using dual-energy X-ray absorptiometry. RESULTS: Compared with controls, fracture cases exhibited reduced serum 25(OH)D and increased PTH, PINP, and CTX, increased femoral subtrochanteric cortical porosity, and reduced cortical thickness and FN aBMD (all, p < 0.05). Serum 25(OH)D was not associated with cortical parameters (all, p > 0.10). PTH was associated with increased PINP, CTX, and cortical porosity of the inner transitional zone and reduced trabecular bone volume/tissue volume and FN aBMD (p ranging from 0.003 to 0.054). Decreasing 25(OH)D and increasing PTH were associated with increased odds for fractures, independent of age, height, weight, calcium supplementation, serum calcium, cortical porosity, and thickness. CONCLUSIONS: These data suggest that serum PTH, not 25(OH)D, is associated with increased intracortical bone turnover resulting in trabecularisation of the inner cortical bone; nevertheless, decreasing 25(OH)D) and increasing PTH are associated with fracture risk, independent of cortical porosity and thickness.

International Osteoporosis Foundation and European Calcified Tissue Society Working Group. Recommendations for the screening of adherence to oral bisphosphonates.

Adherence to oral bisphosphonates is low. A screening strategy is proposed based on the response of biochemical markers of bone turnover after 3 months of therapy. If no change is observed, the clinician should reassess the adherence to the treatment and also other potential issues with the drug. INTRODUCTION: Low adherence to oral bisphosphonates is a common problem that jeopardizes the efficacy of treatment of osteoporosis. No clear screening strategy for the assessment of compliance is widely accepted in these patients. METHODS: The International Osteoporosis Foundation and the European Calcified Tissue Society have convened a working group to propose a screening strategy to detect a lack of adherence to these drugs. The question to answer was whether the bone turnover markers (BTMs) PINP and CTX can be used to identify low adherence in patients with postmenopausal osteoporosis initiating oral bisphosphonates for osteoporosis. The findings of the TRIO study specifically address this question and were used as the basis for testing the hypothesis. RESULTS: Based on the findings of the TRIO study, specifically addressing this question, the working group recommends measuring PINP and CTX at baseline and 3 months after starting therapy to check for a decrease above the least significant change (decrease of more than 38% for PINP and 56% for CTX). Detection rate for the measurement of PINP is 84%, for CTX 87% and, if variation in at least one is considered when measuring both, the level of detection is 94.5%. CONCLUSIONS: If a significant decrease is observed, the treatment can continue, but if no decrease occurs, the clinician should reassess to identify problems with the treatment, mainly low adherence.

Vitamin D and calcium supplementation for three years in postmenopausal osteoporosis significantly alters bone mineral and organic matrix quality.

Prospective, controlled clinical trials in postmenopausal osteoporosis typically compare effects of an active drug with placebo in addition to vitamin D and calcium supplementation in both treatment arms. While clinical benefits are documented, the effect of this supplementation in the placebo arm and in clinical practice on bone material composition properties is unknown. The purpose of the present study was to evaluate these bone quality indices (specifically mineral/matrix, nanoporosity, glycosaminoglycan content, mineral maturity/crystallinity, and pyridinoline content) in patients that either received long-term vitamin D (400-1200IU) and calcium (1.0-1.5g) supplementation, or did not. We have analyzed by Raman microspectroscopy the bone forming trabecular surfaces of iliac crest in pre-treatment samples of a teriparatide study and the endpoint biopsies of the control arm obtained from the HORIZON trial. In general, the mineral/matrix ratio and the glycosaminoglycan (GAG) content was higher while nanoporosity, (a surrogate for tissue water content), the mineral maturity/crystallinity (MMC) and the pyridinoline (Pyd) content was lower in patients without long-term supplementation. Moreover, all indices were significantly dependent on tissue age. In conclusion, vitamin D and calcium supplementation is associated with altered mineral and organic matrix properties.

Effects of the peroxisome proliferator-activated receptor (PPAR)-δ agonist GW501516 on bone and muscle in ovariectomized rats.

Estrogen deficiency promotes bone loss and skeletal muscle dysfunction. Peroxisome proliferator-activated receptors (PPARs) have 3 subtypes (α, δ, and γ). PPARγ agonists induce bone loss, whereas PPARα agonists increase bone mass. Although PPARδ agonists are known to influence skeletal muscle metabolism, the skeletal effects are unsettled. This study investigated the musculoskeletal effects of the PPARδ agonist GW501516 in ovariectomized (OVX) rats. Female Sprague Dawley rats, 12 weeks of age, were allocated to a sham-operated group and 3 OVX groups; high-dose GW501516 (OVX-GW5), low-dose GW501516 (OVX-GW1), and a control group (OVX-CTR), respectively (n = 12 per group). Animals received GW501516 or vehicle (methylcellulose) daily for 4 months by gavage. Bone mineral density (BMD) was assessed by dual x-ray absorptiometry at the femur, spine, and whole body. Bone microarchitecture at the proximal tibia was assessed by microcomputed tomography, and dynamic histomorphometry was performed. Quadriceps muscle morphology and the relative expression of mitochondrial proteins were analyzed. Bone metabolism markers and metabolic markers were measured in plasma. After 4 months, the OVX-GW5 group displayed lower femoral BMD than OVX-CTR. Trabecular separation was higher in the GW-treated groups, compared with OVX-CTR. The OVX-GW5 group also exhibited lower cortical area fraction and a higher structure model index than OVX-CTR. These effects coincided with impaired bone formation in both GW groups. The OVX-GW5 group displayed elevated triglyceride levels and reduced adiponectin levels, whereas no effects on muscle morphology or mitochondrial gene expression appeared. In summary, the PPARδ agonist GW501516 negatively affected bone properties in OVX rats, whereas no effects were detected in skeletal muscle.

Hypovitaminosis D myopathy without biochemical signs of osteomalacic bone involvement.

The aims of this study were to investigate myopathy in relation to vitamin D status, and to study the muscular effects of vitamin D treatment on vitamin D-deficient individuals. Further, hypovitaminosis D myopathy was investigated in relation to alkaline phosphatase (ALP), the most commonly used marker for hypovitaminosis D osteopathy. Eight patients with osteomalacia had an isokinetic dynamometer test of all major muscle groups before and after 3 months of vitamin D treatment. The most pronounced improvements in muscle power were seen in the weight-bearing antigravity muscles of the lower limbs. A cross-sectional study was performed among 55 vitamin D-deficient veiled Arab women living in Denmark and 22 Danish controls. An isometric dynamometer model was used for determination of quadriceps muscle power. Both maximal voluntary contraction (MVC) and electrically stimulated values (single twitch, maximal production rate (MPR), and maximal relaxation rate (MRR)) were determined. The women underwent high-dose vitamin D treatment and were retested after 3 and 6 months. Prior to vitamin D treatment all parameters of muscle function in the group of vitamin D-deficient Arab women were significantly reduced compared with Danish controls. MVC: 259.4 +/- 11.0 N (Newton) versus 392.6 +/- 11. 4 N (P < 10(-6)), single twitch: 47.0 +/- 1.8 N versus 74.6 +/- 2.2 N (P < 10(-5)), MPR 8.9 +/- 0.3 N/10 ms versus 14.3 +/- 0.4 N/10 ms (P < 10(-6)), MRR 4.5 +/- 0.2 N/10 ms versus 6.2 +/- 0.2 N/10 ms (P < 10(-6)). Muscle function was affected to a similar degree in women with and without bone involvement (as indicated by elevated ALP). After 3 months of vitamin D treatment all muscle-related parameters improved significantly. After 6 months only MVC was reduced compared with Danish controls (320.7 +/- 14.3 N (P < 0.02)), whereas all other measurements were normalized. Hypovitaminosis D myopathy is a prominent symptom of vitamin D deficiency, and severely impaired muscle function may be present even before biochemical signs of bone disease develop. Full normalization of hypovitaminosis D myopathy demands high-dose vitamin D treatment for 6 months or more. Our findings indicate that serum levels of ALP cannot be used in the screening for hypovitaminosis D myopathy. Assessment of s-25OHD is the only reliable test.

Commonly recommended daily intake of vitamin D is not sufficient if sunlight exposure is limited.

OBJECTIVES: Sunlight exposure of the skin is known to be the most important source of vitamin D. The aims of this study were: (i) to estimate vitamin D status amongst sunlight-deprived individuals (veiled Arab women, veiled ethnic Danish Moslem women and Danish controls); and (ii) through food intake analysis to estimate the oral intake of vitamin D necessary to keep a normal vitamin D status in sunlight-deprived individuals. DESIGN: Cross-sectional study amongst randomly selected Moslem women of Arab origin living in Denmark. Age-matched Danish women were included as controls. To control for racial differences, a group of veiled ethnic Danish Moslem women (all Caucasians) was included. SETTING: Primary Health Care Centre, City Vest and Department of Endocrinology and Metabolism C, University Hospital of Aarhus, Aarhus Amtssygehus, Aarhus, Denmark. SUBJECTS: Sixty-nine Arab women (60 veiled, nine non-veiled) and 44 age-matched Danish controls were randomly selected amongst patients contacting the primary health care centre for reasons other than vitamin D deficiency. Ten ethnic Danish Moslem women were included through a direct contact with their community. MAIN OUTCOME MEASURES: Serum levels of 25-hydroxyvitamin D were used as estimates of vitamin D status. Intact parathyroid hormone (PTH) was used to control for secondary hyperparathyroidism. Alkaline phosphatase and bone-specific alkaline phosphatase were used as markers for osteomalacic bone involvement. Oral intake of vitamin D and calcium were estimated through a historical food intake interview performed by a trained clinical dietician. RESULTS: Veiled Arab women displayed extremely low values of 25-hydroxyvitamin D: 7.1 +/- 1.1 nmol L-1, compared with 17.5 +/- 2. 3 (P < 0.002) in ethnic Danish Moslems and 47.1 +/- 4.6 (P < 10-17) in Danish controls. PTH was increased amongst veiled Arab women: 15. 6 +/- 1.8 pmol L-1, compared with 5.7 +/- 1.4 in ethnic Danish Moslems and 2.7 +/- 0.3 (P < 10-6) in Danish controls. The vitamin D intake (including food supplementation) was very low amongst Arab women: 1.04 microg day-1, compared with 13.53 amongst ethnic Danish Moslems and 7.49 amongst Danish controls (P < 0.0005). CONCLUSIONS: Severe vitamin D deficiency is prevalent amongst sunlight-deprived individuals living in Denmark. In veiled Arab women, vitamin D deficiency is the result of a combination of limitations in sunlight exposure and a low oral intake of vitamin D. The oral intake of vitamin D amongst veiled ethnic Danish Moslems was, however, very high, at 13.53 microgram (approximately 600 IU), but they were still vitamin D-deficient. Our results suggest that the daily oral intake of vitamin D in sunlight-deprived individuals should exceed 600 IU; most probably it should be 1000 IU day-1 to secure a normal level of 25-hydroxyvitamin D. This finding is in contrast with the commonly used RDA (recommended daily allowance) for adults in Europe: 200 IU day-1.

[Vitamin D deficiency. Easy to diagnose, often overlooked]. / D-vitaminmangel. Let at diagnosticere, ofte overset.

On the basis of five cases the typical clinical picture of patients with severe vitamin D deficiency is presented. The diagnosis can easily be mistaken and it is not uncommon that rheumatic or malignant diseases are suspected instead. By using a simple screening blood test consisting of 25-OH-vitamin D, PTH and alkaline phosphatase most cases will be diagnosed correctly. Important risk factors are reviewed, the most important being: elderly > 70 years, persons with low exposure to direct sunlight, gastrointestinal diseases and persons in anti-convulsive treatment. A treatment regimen consisting of oral supplementation of 1000-1500 mg calcium + 1000 IU vitamin D to patients with an isolated low 25-OH-vitamin D (< 20 nmol/l) is recommended. If the patient also has raised values of PTH or alkaline phosphatase an intramuscular dose of 100,000 IU ergocalciferol pr week for one month is given.

[Prevention in general practice. Are female and male patients treated the same way? A questionnaire study]. / Sygdomsforebyggelse i almen praksis. Gøres der forskel på kvinder og maend? En spørgeskemaundersøgelse.

Three hundred and seventy-four general practitioners (GPs) in Denmark filled in a questionnaire on practices regarding prevention of coronary heart disease (CHD), cancer, osteoporosis, and overweight/underweight. Half of the GPs were questioned about the issue of prevention based upon female case stories and the other half on male case stories with identical wording. The GPs more often in relation to: Prevention of CHD gave dietary counselling and recommended weight loss to slightly overweight male than female patients. Prevention of cancers gave dietary counselling and recommended weight loss and increase of exercise to female than to male patients. Prevention of osteoporosis recommended a supplement of calcium and vitamin D to female than to male patients. Treatment of underweight recommended weight gain and discussion of psycho-social issues to underweight female than male patients. In conclusion, GPs distinguish between men and women in relation to prevention strategies in general practice. There is a need for well-described prevention and action strategies with relevant gender differentiation for use in general practice.

Importance of diet and sex in prevention of coronary artery disease, cancer, osteoporosis, and overweight or underweight: a study of attitudes and practices of Danish primary care physicians.

General practitioners (GPs) in Denmark (n = 374) answered a questionnaire on attitudes toward including information on diet and sex in the prevention of coronary artery disease, cancers, osteoporosis, and weight problems. Risk factors for disease were ranked as follows: smoking, alcohol, stress, diet, physical exercise, heredity, and hygiene. Patients' lack of motivation, insufficient time for each patient, and inadequate knowledge about nutrition were listed by GPs as barriers to dietary counseling. GPs stated that the sex of the patient was important only for counseling on osteoporosis. Lack of time and insufficient knowledge were perceived as barriers to including sex-specific issues in prevention. One-half of the GPs were questioned about the issue of prevention on the basis of female case stories and the other half on the basis of male case stories with identical wording. Responses to the case stories indicated that GPs would give dietary guidance and recommend loss of weight to slightly overweight male patients to a much greater degree than to overweight female patients for prevention of coronary artery disease, give dietary counseling and recommend loss of weight and exercise to female patients more than to male patients for prevention of cancers, recommend a supplement of calcium and vitamin D for prevention of osteoporosis to female patients, and recommend weight gain and discuss psychosocial issues more with underweight female patients than with underweight male patients. Female GPs included measures of prevention such as dietary counseling, exercise prescription, dietary supplement prescription, and discussion of psychosocial issues to a greater extent than did male GPs.

[Glucocorticoid-induced osteopenia]. / Glukokortikoidinduceret osteopeni.

This article reviews the pathogenesis of glucocorticoid-induced osteopenia (GIO). GIO is a result of direct and indirect mechanisms leading to: 1) decreased intestinal calcium absorption, 2) decreased renal calcium reabsorption, 3) increased osteoclast activity with increased bone resorption, 4) decreased osteoclast activity with decreased bone formation. The mainly osteoclast activity is raised on the basis of secondary hyperparathyroidism. The different possible treatments in order to prevent GIO are reviewed on the basis of the results of the most important studies about the subject. We conclude that before a secure recommendation about prophylactic treatment can be made more prospective studies with fracture incidence as a measure should be made. However, on the basis of the studies that have already been made, it seems rational to give patients in longterm glucocorticoid treatment a calcium supplement of 0.5-1 g/day either in tablet form or by changing the diet, combined with a vitamin-D supply: either ergocalciferol 600-800 IU/day (e.g. in the form of 2 multivitamin tabs/day) or calcitriol 0.5 microgram/day.

Osteopenia and osteomalacia after gastrectomy: interrelations between biochemical markers of bone remodelling, vitamin D metabolites, and bone histomorphometry.

The prevalence of metabolic disease in a population of 68 postgastrectomy patients was assessed using histomorphometric evaluation of transiliac bone biopsy specimens after tetracycline double labelling. Trabecular bone volume was significantly lower in the postgastrectomy group (p less than 0.01): 62% of the patients had increased osteoid surface, 56% increased osteoid thickness, and 24% increased mineralisation lag time. Only 18%, however, fulfilled the diagnostic criteria for osteomalacia--increased osteoid thickness and increased mineralisation lag time. Postgastrectomy patients had reduced serum concentrations of calcium (p less than 0.01), phosphate (p less than 0.01), and 25-hydroxyvitamin D, while levels of alkaline phosphatase and 1,25 dihydroxyvitamin D were high (p less than 0.01). The severity of the mineralisation defect as reflected by mineralisation lag time was positively correlated to serum 25-hydroxyvitamin D, but unrelated to serum 1,25-dihydroxyvitamin D. Multiple linear regression analysis showed that serum 25-hydroxyvitamin D, age, and the duration of postoperative follow up were significant determinants of the mineralisation defect in a given patient. The limited value of serum markers in the diagnosis of osteomalacia was emphasised by the fact that six of the eight patients with osteomalacia had normal serum levels of calcium and alkaline phosphatase, and five of the eight had values for 25-hydroxyvitamin D in the normal range for healthy control subjects. The results clearly show the need for vitamin D supplementation and regular control after gastric resection.

Dermal, intestinal, and renal obligatory losses of calcium: relation to skeletal calcium loss.

Calcium balance is the difference between dietary calcium intake on the one hand and dermal, fecal, and urinary losses on the other. Bone is lost throughout adult life by at least three different mechanisms. Whether all these processes are affected by dietary calcium is at present unknown. In case they are not, dietary calcium intake should balance an adjusted value estimated as obligatory skeletal calcium loss minus obligatory external (dermal + intestinal + urinary) calcium loss. Such a correction would reduce estimated calcium allowances. To solve this question it is important, however, to ascertain whether obligatory bone loss is affected by dietary intake of calcium, ie, Can a high dietary calcium or calcium supplementation influence bone metabolism and reduce bone loss at all ages?

The effects of etidronate on trabecular bone remodeling in postmenopausal spinal osteoporosis: a randomized study comparing intermittent treatment and an ADFR regime.

Thirty-seven patients were randomized to receive intermittent cyclic etidronate (400 mg/day oral for 2 weeks, followed by 13 weeks off treatment) or an ADFR treatment (100 micrograms/day oral triiodothyronine for 7 days, followed by 400 mg/day etidronate for 2 weeks and 12 weeks off treatment). Supplemental calcium (120 mg/day) and vitamin D3 (400 IU/day) were given throughout the study period to all patients. Biochemical analyses, iliac-crest bone biopsies, and lumbar bone mineral content (BMC) measurements were performed before and during 60 weeks of treatment. Sixteen patients in the intermittent cyclic etidronate group and 15 in the ADFR group completed 60 weeks of treatment. Serum alkaline phosphatase decreased from 185 (43) (mean, (SD] to 144 (35) (p less than 0.001) and from 221 (69) to 156 (43) (p less than 0.002) during intermittent cyclic etidronate treatment and ADFR treatment, respectively, without any significant changes in renal hydroxyproline excretion. Final resorption depth, trabecular bone activation frequency, and bone formation rate decreased significantly from 51.5 (48.4/60.0) microns (median (25%/75% quartiles] to 44.0 (39.6/46.2) microns (p less than 0.04), from 0.30 (0.17/0.62) year-1 to 0.10 (0.02/0.19) year-1 (p less than 0.03) and from 0.035 (0.020/0.081) microns3/microns2/day to 0.015 (0.002/0.025) microns3/microns2/day, p less than 0.03 respectively, during intermittent cyclic etidronate treatment, but were unchanged during ADFR treatment. No significant changes in trabecular bone volume, bone balance per remodeling cycle, or BMC were noted in either treatment group; no evidence of osteomalacia was found. Intermittent cyclic etidronate treatment may be effective in preventing bone loss and in decreasing the risk of trabecular plate perforation, and thereby maintaining the integrity of bone architecture, in postmenopausal osteoporosis.(ABSTRACT TRUNCATED AT 250 WORDS)

A randomized study on the effects of estrogen/gestagen or high dose oral calcium on trabecular bone remodeling in postmenopausal osteoporosis.

Thirty-seven patients with postmenopausal crush fracture osteoporosis were randomized to oral cyclic estrogen/gestagen (n = 20) or oral calcium (2000 mg elemental calcium per day) (n = 17). Fourteen in each group completed 1 year of treatment. Iliac crest bone biopsies were obtained after intravital double labeling with tetracycline before and after treatment in 10 patients on estrogen/gestagen and 11 patients on calcium. In the estrogen/gestagen group the activation frequency in trabecular bone decreased from 0.52 + 0.11 (SEM) year-1 to 0.27 + 0.08 year-1 (p less than 0.01). No significant changes were found in resorption or formation periods. The osteoid surfaces and the mineralizing surfaces decreased (p less than 0.05), whereas the decrease in eroded surfaces was insignificant. Furthermore, no significant changes were observed in final resorption depth, wall thickness or bone balance per remodeling cycle. Serum alkaline phosphatase and renal hydroxyproline excretion decreased during treatment (p less than 0.002), whereas the lumbar bone mineral content (BMC) increased (p less than 0.01). In the calcium group the extent and thickness of osteoid surfaces decreased (p less than 0.05) without significant changes in activation frequency. Serum alkaline phosphatase and renal hydroxyproline excretion decreased during treatment (p less than 0.02). No significant changes were observed in lumbar BMC or the other histomorphometric parameters. The study supports that the positive effect of estrogen/gestagen on BMC can be explained by a reduction in the activation frequency of new remodeling cycles leading to a decreased remodeling space and an increase in mean bone age. There is no evidence of a positive balance per remodeling cycle.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of high-dose glucocorticoid administration on serum bone gamma carboxyglutamic acid-containing protein, serum alkaline phosphatase and vitamin D metabolites in normal subjects.

The effects of 40 mg of prednisone given daily for 5 days to normal individuals on serum levels of bone Gla-protein (BGP), alkaline phosphatase, calcium phosphate, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D and immunoreactive parathyroid hormone (S-iPTH) and on renal excretions of calcium, phosphate and hydroxyproline were evaluated in a double-blind, placebo controlled study. In the prednisone group a 75% decrease (P less than 0.001) was found in serum BGP compared to a 6% decrease (P less than 0.05) in serum alkaline phosphatase. The renal hydroxyproline excretion remained unchanged. Serum calcium was unchanged while the fasting urinary calcium excretion showed a 2-fold increase (P less than 0.001). Serum 1,25-dihydroxyvitamin D increased (P less than 0.01) in spite of unchanged serum 25-hydroxyvitamin D, serum phosphate and parathyroid function (as judged by S-iPTH and the maximal tubular reabsorption capacity for phosphate (TmP/GFR]. The data suggest a direct inhibition of osteoblast number and/or function by short-term glucocorticoid administration with unchanged bone resorption leading to a negative bone mineral balance. The increase in serum 1,25-dihydroxyvitamin D is probably due to a direct stimulation by glucocorticoids of the renal 1 alpha-hydroxylase. The effects of the vitamin D metabolite, however seem to be blunted.

The effects of short-term, high-dose treatment with prednisone on the nuclear uptake of 1,25-dihydroxyvitamin D3 in monocytes from normal human subjects.

Animal and cell culture studies indicate glucocorticoid regulation of 1,25-dihydroxyvitamin D3 receptors and interference with cellular effects of vitamin D. These investigations prompted us to examine the effects of prednisone on the nuclear uptake of 1,25-dihydroxyvitamin D3 in freshly isolated human monocytes. Eighteen normal subjects were studied in a randomized, double-blind, placebo-controlled study. Analysis of receptor kinetics revealed that the maximal nuclear uptake (Bmax) of (3H)-1,25-dihydroxyvitamin D3 in monocytes decreased 40% (P less than .001) after prednisone treatment. In the group treated with prednisone (40 mg/d for 5 days) s-1,25-dihydroxyvitamin D increased 46% (P less than .01). S-25-Hydroxyvitamin D, S-phosphat, S-calcium, and S-iPTH remained unchanged. Osteoblastic production of the matrix protein, bone gla protein (BGP) is stimulated by 1,25-dihydroxyvitamin D3. However, despite increased serum levels of 1,25-dihydroxyvitamin D3, the prednisone-treated group revealed a 75% reduction in s-BGP. The present data indicate that corticosteroids decrease the nuclear uptake of 1,25-dihydroxyvitamin D3 in human monocytes. Further investigations are necessary, however, to elucidate the biologic mechanism for this observation and whether the mechanism is operative in other human tissues including bone.