Serum osteocalcin levels and bone alkaline phosphatase isoenzyme after oophorectomy and in primary hyperparathyroidism

Serum osteocalcin levels peaked 1 yr after oophorectomy in a prospective study of 12 women. Estrogen treatment restored serum osteocalcin to the normal range within 4 months of therapy. The changes in serum osteocalcin preceded those in bone alkaline phosphatase activity by 1-2 months, in these oophorectomized patients and during estrogen treatment. The changes in these two markers of bone formation over time were significantly different from those in urinary hydroxyproline excretion. A significant positive correlation was found between bone alkaline phosphatase and serum osteocalcin levels in patients after oophorectomy and in 18 patients with primary hyperparathyroidism. Significant positive correlations also were found between the biochemical indices of osteoblastic function and urinary hydroxyproline excretion and/or nephrogenous cAMP in primary hyperparathyroidism. In most of the patients with primary hyperparathyroidism, however, the elevation in bone alkaline phosphatase was more marked than that in osteocalcin. These data indicate that the clinical utility of serum osteocalcin as a marker of bone formation is similar but not identical to that of bone alkaline phosphatase.     

Castrated men exhibit bone loss: effect of calcitonin treatment on biochemical indices of bone remodeling

To test the hypothesis that the reduction in gonadal function can lead to bone mass loss, a group of 12 men who had undergone bilateral orchidectomy at the age of 28.2 +/- 6.8 yr was evaluated. A progressive loss of the lumbar bone density was observed as a function of time after orchidectomy. Both the biochemical indices of bone resorption (urinary hydroxyproline/creatinine ratio and plasma tartrate-resistant acid phosphatase) and bone formation (serum osteocalcin and bone isoenzyme of alkaline phosphatase) were significantly increased in the patients compared with healthy controls. A positive correlation was found between urinary hydroxyproline excretion and percent change in spinal bone mineral density per yr. Because of this increase in the biochemically indicated bone resorption, nine of the patients were studied again after 1-3 yr and were thereafter treated with intranasal calcitonin. Urinary hydroxyproline excretion normalized after 3 months of treatment, and a significant decrease, but not to normal levels, was also observed in the mean values for the other biochemical indices of bone remodeling. Thus, testosterone deficiency, like estrogen deficiency, is associated with accelerated bone loss. The increase in osteoresorption was partially corrected by calcitonin treatment.     

Correlation of interleukin-6 serum levels with bone density in postmenopausal women

Summary In order to identify possible correlations between interleukin-6 (IL-6) and hormonal and biochemical parameters of bone metabolism, or bone density, 24 postmenopausal women were studied. Serum IL-6, estradiol, calcium, phosphorus, osteocalcin, alkaline phosphatase, the urinary secretion of calcium, phosphoru and hydroxyproline, and bone density of the lumbar spine, femur and radius were measured. No significant correlation was found between IL-6 and the biochemical parameters. A negative correlation was found between IL-6 and serum estradiol, as well as between IL-6 and bone density in 5 out of 6 sites studied. It is possible that women with high IL-6 levels, may develop lower bone mass.     

Skeletal responsiveness to parathyroid hormone in healthy females: relationship to menopause and oestrogen replacement

In order to directly evaluate the role of parathyroid hormone (PTH) and its interaction with oestrogens for postmenopausal bone loss, studies were performed where synthetic human (1-38) PTH was infused s.c. over 24 h in 15 healthy females. Measurements were made of serum electrolytes, PTH and biochemical indices of bone turnover: serum osteocalcin and alkaline phosphatase and fasting urinary hydroxyproline and calcium. During the infusion of PTH there were significant increases of serum calcium (15%), fasting urinary calcium (55%) and hydroxyproline (80%) but a reduction of the serum osteocalcin concentrations (15%). There were significant relations between the calcaemic response and the increases of urinary calcium and hydroxyproline and the two latter were also closely related. There was, however, no correlation between the responses to PTH for the formative vs the resorptive indices. Postmenopausal women displayed greater increases of serum calcium and fasting urinary hydroxyproline indicating greater skeletal sensitivity to exogenous PTH. Following treatment with oestrogens the indices of skeletal responsiveness were reversed towards the premenopausal values. The findings demonstrate that during short-term infusion of PTH there is a dissociation between bone resorption and formation and, furthermore, that the menopause is associated with an enhanced skeletal sensitivity for PTH.     

Age and menopause-related changes in indices of bone turnover

Age-related bone loss has been attributed to a decline in bone formation due to decreased osteoblast function. However, studies examining the relationship between age or menopausal status and indices of bone formation such as serum osteocalcin have yielded conflicting results. To examine these relationships we studied indices of bone formation and resorption and bone mineral density in 247 normal women, including 96 postmenopausal women ranging in age from 20-75 yr. A cubic polynomial regression best fit the relationship between age and serum osteocalcin (r = 0.32; n = 228; P = 0.0001) and urinary hydroxyproline/creatinine excretion (r = 0.40; n = 228; P = 0.0001), with both indices declining before the menopause, rising at the menopause, and subsequently falling through the seventh and eighth decades. While a significant decline in osteocalcin levels was observed in the postmenopausal group older than 60 yr, levels in subjects older than 60 yr remained higher (+31%) than those in late premenopausal subjects. Urinary calcium to creatinine excretion rose in the premenopausal years, increased markedly after the menopause, and remained at this level subsequently. Urinary hydroxyproline/creatinine, but not serum osteocalcin or urinary calcium/creatinine excretion, was a significant predictor of bone mineral density at the lumbar spine and the femoral neck independent of age. These data are consistent with the hypothesis that age-related bone loss after the menopause occurs in the presence of initially increased but subsequently decreasing bone turnover with maintenance of a relative excess of bone resorption.     

Long term effects of dichloromethylene diphosphonate in Paget's disease of bone

Dichloromethylene diphosphonate (Cl2MDP) is a diphosphonate which markedly inhibits bone resorption. We have tested Cl2MDP in Paget's disease, a disorder characterized by increased bone remodeling. Sixty-three patients with progressive Paget's disease were treated for 6 months with Cl2MDP at daily oral doses of 400, 800, 1600, or 2400 mg. Thirty-nine patients received calcium and vitamin D supplements during treatment. patients in all treatment groups had significant reduction in serum alkaline phosphatase, urinary hydroxyproline, skeletal uptake of 99mtechnetium-diphosphonate scintiscans, and resorption parameters on iliac crest biopsy samples as assessed by quantitative histomorphometry. Treatment was well tolerated and did not induce a skeletal mineralization defect. The reduction in alkaline phosphatase and urinary hydroxyproline persisted 1 yr after withdrawal of treatment. The biochemical remission was sustained in half of the patients 2 yr after the end of treatment and was accompanied by a marked reduction of bone pain. a daily dose of 800 mg is recommended as the best of control of clinical and biochemical symptoms. The transient increase in iPTH levels observed in patients treated with Cl2MDP alone did not occur when calcium and vitamin D were added. We conclude that Cl2MDP is effective in the treatment of Paget's disease of bone and provides a prolonged response. Dietary supplementation with calcium and vitamin D is desirable to prevent secondary hyperparathyroidism.     

Insulin-like growth factors I and II: aging and bone density in women

Serum concentrations of insulin-like growth factors (IGF) were measured by RIA in 57 normal women, ages 30 - 90 yr, and in 29 untreated women with postmenopausal osteoporosis and vertebral compression fractures, ages 55 - 75 yr. These values were correlated with bone mineral density (BMD) of the distal and midradius assessed by single photon absorptiometry and of the lumbar spine assessed by dual photon absorptiometry as well as serum and urinary calcium, phosphorus, creatinine, alkaline phosphatase, immunoreactive PTH, urinary hydroxyproline, and creatinine clearance. Serum IGF-I levels declined markedly with age (r = -0.47, P less than 0.001). Serum IGF-II levels decreased only slightly with age, and this decrease was not statistically significant. Although BMD at all three scanning sites also declined significantly with age, neither serum IGF-I nor II concentrations correlated with BMD when age was held constant. In women with postmenopausal osteoporosis, serum IGF-I and II did not differ from the concentrations in normal women of similar age and did not correlate with BMD. In neither group was a correlation between serum IGF-I or II and serum or urinary proteins or cations found. Thus, there was no evidence that impaired synthesis of IGF-I and II contributes to pathogenesis of the syndrome of Type I (postmenopausal) osteoporosis, which is characterized by accelerated loss of trabecular bone and vertebral compression fractures. The possibility remains, however, that decreasing concentrations of serum IGF-I play a role in the more gradual loss of bone with aging (Type II osteoporosis) in which impared bone formation at the cellular level has been demonstrated.     

Effect of low-dose prednisone (with calcium and calcitriol supplementation) on calcium and bone metabolism in healthy volunteers

The administration of moderate to high doses of corticosteroids is associated with bone loss. This probably results from the uncoupling of bone formation (decreased) and bone resorption (unchanged or increased). We examined the effect of low-dose (10 mg/day) prednisone (LDP) and the possible mitigating effects of calcium and 1.25 (OH)2 vitamin D (calcitriol) on calcium and bone metabolism in eight healthy, young male volunteers. The study consisted of four observation periods: in the first period, LDP was prescribed during 1 week; in the second, third and fourth periods, calcium (500 mg/day), calcitriol (0.5 micrograms b.i.d.) and calcium in combination with calcitriol, respectively, were added to LDP. Bone formation was measured by means of serum osteocalcin, carboxy-terminal propeptide of type 1 procollagen (P1CP) and alkaline phosphatase, bone resorption by means of urinary excretion of calcium, hydroxyproline, (free and total) pyridinoline, (free and total) deoxypyridinoline and serum carboxy-terminal cross- linked telopeptide of type 1 collagen (1CTP). Dietary calcium and sodium intake were maintained at a stable level during the entire study period. Treatment with LDP led to a decrease in osteocalcin, P1CP and alkaline phosphatase (all P < 0.01). Urinary excretion of pyridinolines, hydroxyproline and serum 1CTP did not increase, but remained unchanged or slightly reduced (P < 0.05), depending on the time of measurement and the marker of bone resorption. Parathyroid hormone (PTH) (insignificantly) increased during LDP (+19%) and LDP plus calcium (+14%), but decreased during supplementation with calcitriol (-16%) and calcium/calcitriol (-44%; P < 0.01). Urinary excretion of calcium increased during treatment with LDP and calcitriol (P < 0.05) and calcium/calcitriol (P < 0.05). It is concluded that LDP has a negative effect on bone metabolism, since bone formation decreased while bone resorption remained unchanged or decreased slightly. The increase in PTH during LDP could be prevented by calcitriol combined with calcium supplementation.      

The effect of carbonic anhydrase inhibition on calcium and bone homeostasis in healthy postmenopausal women

Carbonic anhydrase localized in bone resorptive cells generates the protons necessary for bone resorption. Inhibition of the enzyme is a potential mechanism for decreasing bone resorption. Eight healthy post-menopausal women received oral acetazolamide 250 mg twice daily for 28 d. Bone resorption, evaluated by serum acid phosphatase activity and the renal excretion of hydroxyproline, was unaltered, as was bone formation estimated by serum levels of alkaline phosphatase and osteocalcin. The fasting renal excretion of calcium was increased, whereas serum ionized calcium was unchanged. The maximal renal reabsorption of phosphate decreased, but it was not an effect of PTH as it decreased significantly during the treatment period. In conclusion, no significant effect on biochemical markers of bone remodelling could be detected during the study period. The observed changes in calcium and phosphate metabolism may be secondary to the renal effect of acetazolamide.     

Effects of various antireabsorptive treatments on bone mineral density in hypogonadal young women after allogeneic stem cell transplantation

Ovarian failure after allogeneic stem cell transplant (allo-SCT) is an important risk factor for development of osteoporosis. We investigated the effects of various antiresorptive treatments in long-term surviving females with ovarian failure after allo-SCT. A total of 60 women with osteoporosis or osteopenia were divided randomly into four groups of 15 women each. Group 1 was treated with calcium and vitamin D alone, group 2 received the same treatment in combination with hormone replacement therapy (HRT), group 3 received risedronate (35 mg weekly, orally for 1 year) and group 4 zoledronic acid (3 monthly doses of 4 mg (intravenous)). All groups were similar for age, body mass index, underlying disease and time elapsed from transplant. Lumbar and femoral bone mineral density (BMD) were measured at baseline and after 12 months, together with serum osteocalcin and urinary hydroxyproline. At 12 months, a significant decrease in lumbar and femoral BMD was observed in group 1 and a milder decrease in group 2. Risedronate treatment increased significantly lumbar BMD and prevented bone loss at the femoral neck. Zoledronic acid increased significantly both lumbar and femoral BMD. In groups 3 and 4 the hydroxyproline excretion was significantly reduced, while osteocalcin mildly increased only in group 4. In conclusion, bisphosphonate administration is useful to prevent and treat bone demineralization in young adult women after allo-SCT.     

Changes in bone turnover in young women consuming different levels of dietary protein

Although high protein diets are known to increase urinary calcium excretion and induce negative calcium balance, the impact of dietary protein on bone turnover and fractures is controversial. We therefore evaluated the effect of dietary protein on markers of bone turnover in 16 healthy young women. The experiment consisted of 2 weeks of a well balanced diet containing moderate amounts of calcium, sodium, and protein followed by 4 days of an experimental diet containing one of three levels of protein (low, medium, or high). On day 4, serum and urinary calcium, serum PTH, 1,25-dihydroxyvitamin D, serum osteocalcin, bone-specific alkaline phosphatase, and urinary N-telopeptide excretion were measured. Urinary calcium excretion was significantly higher on the high than on the low protein diet. Secondary hyperparathyroidism occurred on the low protein diet. Urinary N-telopeptide excretion was significantly greater during the high protein than during the low protein intake (48.2 +/- 7.2 vs. 32.7 +/- 5.3 nM bone collagen equivalents/mM creatinine; P < 0.05). There was no increase in osteocalcin or bone-specific alkaline phosphatase when comparing the low to the high diet, suggesting that bone resorption was increased without a compensatory increase in bone formation. Our data suggest that at high levels of dietary protein, at least a portion of the increase in urinary calcium reflects increased bone resorption.     

Prevention of postmenopausal bone loss in rheumatoid arthritis patients. A two-year prospective study

The effect of three different therapeutic regimens on bone mineral content at the radius and lumbar spine was studied in a group of 60 postmenopausal rheumatoid arthritis patients. Results were compared to those in a group of controls matched for sex, age, disease duration and menopausal state. Serum and urinary parameters of calcium metabolism were also evaluated in the three treatment groups. The three treatment regimens were: 1 alpha hydroxyvitamin D + calcium + placebo; 1 alpha hydroxyvitamin D + calcium + lynestrenol; and 1 alpha hydroxyvitamin D + calcium + sodium fluoride. In all treatment groups there was a positive effect of therapy compared to controls, though this was only significant in the 1 alpha hydroxyvitamin D + calcium + lynestrenol group at the axial skeleton after 1 and 2 years of treatment. Serum calcium rose significantly in the 1 alpha hydroxyvitamin D + calcium + placebo group and serum creatinin was raised in all the treatment groups during therapy. In the 1 alpha hydroxyvitamin D + calcium + lynestrenol group, serum alkaline phosphatase activity and urinary hydroxyproline excretion decreased significantly.     

Effect of a single infusion of aminohydroxypropylidene on calcium and bone metabolism in healthy volunteers monitored during 2 months

Recently, bisphosphonates have been used to prevent postmenopausal bone loss. As the effects of bisphosphonates on normal bone metabolism are unknown, 3-amino-1-hydroxypropylidene-1,1-diphosphonate (APD) was studied in healthy subjects. The effects of a single 20-mg APD infusion on biochemical parameters of calcium and bone metabolism were investigated during 2 months in 10 healthy male volunteers. This single moderate dose of APD reduced biochemical parameters of bone resorption during the time of follow-up. After 2 months, urinary hydroxyproline excretion was still below the basal level. The decreased serum calcium levels did not return to basal values. Biochemical parameters of bone formation, serum alkaline phosphatase and osteocalcin, showed a slight increase during the first month after stimulation of the parathyroids and a corresponding increase in serum 1,25-dihydroxyvitamin D. These formation parameters decreased thereafter, probably representing coupling between bone resorption and bone formation.     

Additional beneficial effects of alendronate in growth hormone (GH)-deficient adults with osteoporosis receiving long-term recombinant human GH replacement therapy: a randomized controlled trial.

We conducted a randomized controlled trial in osteoporotic adult GH-deficient (GHD) patients to assess whether additional treatment with a bisphosphonate would further favorably influence parameters of bone turnover and bone mineral density measurements (BMD). All patients were receiving stable recombinant human (rhGH) replacement therapy for 4 yr at the start of the study. Eighteen GHD patients with osteoporosis were randomized to continue their rhGH maintenance dose or to receive combination therapy with rhGH and alendronate for 12 months. All patients were calcium and vitamin replete, and there were no changes in calcium, vitamin D, or hormone replacement therapy for the duration of the study. At baseline there were no significant differences between the alendronate and the control group in parameters of bone turnover, BMD, or prevalence of vertebral fractures. Childhood-onset and adult-onset GHD were equally distributed between the groups, with no statistical differences in age and gender or other parameters between groups. Mean serum osteocalcin, serum bone-specific alkaline phosphatase, and urinary N-telopeptide/creatinine ratio were within the normal range at the start of the study. In the alendronate group all measured parameters of bone turnover, i.e. bone-specific alkaline phosphatase, osteocalcin, and urinary N-telopeptide/creatinine ratio, significantly decreased after 6 months, with no further decrease thereafter. No changes were observed in the control group. In the alendronate-treated patients serum bone-specific alkaline phosphatase decreased from 10.9 +/- 0.9 to 6.8 +/- 0.7 microg/L at 6 months (P < 0.001), serum osteocalcin decreased from 3.9 +/- 0.4 to 1.7 +/- 0.3 microg/L (P < 0.001), and the urinary N-telopeptide/creatinine ratio decreased from 27.3 +/- 7.0 to 6.4 +/- 0.8 nmol/mmol (P = 0.01). In this group, lumbar spine BMD significantly increased from baseline by 3.4% at 6 months (P = 0.001) and by 4.4% at 12 months (P < 0.001) of treatment, with no further significant increase between 6 and 12 months (P = 0.217). No changes in lumbar spine BMD were observed in the control group. There were no significant changes in femoral neck BMD in either group for the duration of the study. No incident vertebral or peripheral fractures were documented in either group at the end of the study. In summary, this is the first report indicating that treatment with alendronate was able to significantly increase BMD at the lumbar spine in GHD patients with osteoporosis receiving stable rhGH replacement for 4 yr. This increase was significantly greater in alendronate-treated patients than in patients maintained on rhGH. The increase in lumbar spine BMD in the alendronate-treated patients was associated with a decrease in the measured markers of bone turnover, whereas these markers did not change further in the patients maintained on rhGH. This controlled study suggests that additional treatment with alendronate in GHD patients with osteoporosis receiving stable rhGH replacement therapy is effective in increasing BMD at the lumbar spine. Further investigation is required to assess whether rhGH replacement alone or combined treatment with rhGH and alendronate is able to reduce the increased fracture risk associated with GHD.     

Hypercalcemia and hyperphosphatemia in thyrotoxoicosis and the therapeutic effect of propranolol

Measured levels of serum calcium, phosphate, alkaline phosphatase, and urinary hydroxyproline were measured and calcium-phosphate product was calculated in 20 hyperthyroid patients and 20 normal controls. Eleven of the patients took propranolol 160 mg per day for 28 days. We found that the serum level of calcium was higher than that of normal controls. The incidence of hypercalcaemia in hyperthyroid patients was 10%. The serum level of phosphate and the calcium-phosphate product increased (P less than 0.01). Elevation of alkaline phosphatase and bone alkaline phosphatase were also observed (P less than 0.01). The urinary hydroxyproline was also elevated (P less than 0.01). After treatment with propranolol serum calcium and triiodothyronine decreased (P less than 0.05). It is suggested that the major mechanism of hypercalcaemia and hyperphosphatemia in hyperthyroidism was increase of bone absorption stimulated by triiodothyronine. Propranolol decreased the serum level of calcium through decreasing triiodothyronine level and through beta-receptor blocking effect as well as its direct effect on bone.     

Serum osteocalcin and total body calcium in normal pre- and postmenopausal women and postmenopausal osteoporotic patients

Serum osteocalcin was measured in 51 normal pre- and 114 postmenopausal women and in 41 postmenopausal osteoporotic patients. Total body calcium (TBCa) was determined in the same individuals by neutron activation analysis. Many of the perimenopausal nonosteoporotic women had increased serum osteocalcin values, but 15 yr or more after the menopause most of the women had serum osteocalcin levels in the normal range. Comparing normal women before and after menopause, the mean serum osteocalcin levels [7.8 +/- 4.7 (+/- SE) and 10.1 +/- 9.4 ng/mL] were not significantly different; however, the TBCa values (898 +/- 99 and 806 +/- 111 g) were significantly different (P less than 0.001). When the normal postmenopausal women were regrouped according to high vs. low osteocalcin values, TBCa and phosphorus content as well as forearm linear bone density were significantly lower in the high osteocalcin group, even though most of the other variables, including urinary hydroxyproline excretion, serum alkaline phosphatase, age, height, and weight, were not different. Osteoporotic women had a mean serum osteocalcin concentration of 17.4 +/- 8.6 ng/ml and a TBCa of 657 +/- 83 g, both significantly different from the respective values in normal and pre- and postmenopausal women (P less than 0.001 for both variables in comparison to each group). These data suggest that high serum osteocalcin levels, at least on a group basis, are an index of low skeletal mass.     

Short and long-term effects of growth hormone treatment on bone turnover and bone mineral content in adult growth hormone-deficient males*

OBJECTIVE In view of the fact that GH-deficient adults present with pronounced osteopaenia and can be considered at risk for osteoporotic fractures, we wanted to investigate the effects of biosynthetic GH replacement therapy (0.25 IU/kg/week) on biochemical indices of bone turnover and on bone mineral content (BMC) in a group of GH-deficient adult males. DESIGN We performed a 6-month randomized, double-blind, placebo-controlled study, followed by 12–24 months of GH treatment in all patients. PATIENTS Twenty adult males with GH deficiency of childhood onset were studied. MEASUREMENTS We measured serum IGF-I, serum phosphate, biochemical indices of bone turnover (serum alkaline phosphatase activity, serum osteocalcin, serum carboxyterminal propeptide of type-I procollagen, fasting urinary hydroxyproline/creatinine and calcium/creatinine ratios) and bone mineral content, measured at the forearm and the lumbar spine by single and dual-photon absorptiometry respectively. RESULTS After 3 and 6 months of GH administration, the serum levels of alkaline phosphatase, osteocalcin and carboxyterminal propeptide of type-I procollagen, and the fasting urinary hydroxyproline/creatinine ratio were significantly increased compared to placebo-treated patients (P<0.01 to P<0.001). During the open study phase, the values for these indices of bone turnover remained elevated above pretreatment levels (P<0 01 to P<0 001 at 12 months), a downward trend becoming apparent after about one year of GH treatment. BMC values showed an initial decline after 3 months of GH treatment (most likely due to an expansion of the remodelling space), followed by a significant and progressive increase above pretreatment values, reaching 7–8% for total BMC at the lumbar spine (L2-L4) and 9–9% for total BMC at the forearm, after 30 months of GH administration. CONCLUSIONS The data of our study show that administration of substitutive doses of growth hormone to GH-deficient adult males activates bone turnover for a period of at least one year and suggests that this may have a beneficial effect on bone mass in these patients.     

Effect of fluoride therapy on nondialyzable urinary hydroxyproline,serum alkaline phosphatase,parathyroid hormone,and 25-hydroxyvitamin D

The effect of sodium fluoride therapy was studied in 40 osteoporotic male subjects, aged 50–80 yr. Twenty patients were treated with sodium fluoride (20–40 mg/day) and 20 received placebo for 107 wk. A marked increase (53%; p < 0.001) in the nondialyzable fraction of urinary hydroxyproline was found in the fluoridetreated group. Total urinary hydroxyproline levels were unchanged. The increased fraction of urinary hydroxyproline is suggestive of increased bone collagen synthesis and is consistent with the finding of a diminished rate of bone loss in the fluoride-treated group (per cent change in bone density after 107 wk was ?0.14 ± 5.28 versus ?5.24 ± 7.62 for the placebo-treated group; p < 0.02). Serum alkaline phosphatase levels were elevated in the fluoride-treated group (38%; p < 0.001) after 107 wk of treatment. This change, as well as the increased fraction of urinary hydroxyproline persisted for at least 6 mo after cessation of fluoride treatment and was not temporally related to serum fluoride levels. No significant changes in serum parathyroid hormone, 25-hydroxyvitamin D, serum calcium, and phosphorus were found after 1 yr of fluoride treatment. These findings suggest that fluoride does not alter serum 25-hydroxy-vitamin D and that the mechanism by which fluoride increases the rate of bone formation does not involve hyperparathyroidism.     

Effects of a short course of estrogen on mineral metabolism in postmenopausal women

Previous studies suggested that estrogen administration leads to an increase in circulating immunoreactive PTH (iPTH), thought to be secondary to a slight decrease in serum calcium resulting from inhibition of bone resorption. Using three different RIAs, we measured iPTH in serum from 10 postmenopausal women before and after 14 days of ethinyl estradiol administration. In 2 sensitive RIAs directed at the midregion of the PTH molecule, iPTH values fell or remained unchanged in each subject, with average decreases of 23% (P less than 0.001) and 28% (P less than 0.005) in the two assays. Total urinary cAMP, the tubular maximum for urinary phosphate excretion, and serum iPTH measured with the third RIA did not change after estrogen treatment. Fasting urinary calcium and hydroxyproline and serum calcium, phosphorus, albumin, alkaline phosphatase, and osteocalcin all decreased after treatment, and serum 1,25-dihydroxyvitamin D increased in each subject. In a second cohort of 5 women given ethinyl estradiol for 8 weeks, similar changes were found at 2 weeks, but there was a trend toward increasing serum iPTH, increasing total urinary cAMP excretion, and decreasing the tubular maximum for urinary phosphate excretion by 8 weeks. The increase in serum 1,25-dihydroxyvitamin D and the decrease in serum osteocalcin were again found after 2 weeks of estrogen and did not change further despite continued treatment. These results indicate multiple effects of a 2-week course of estrogen treatment on mineral metabolism in the absence of an increase in serum iPTH or several biological indices of PTH activity.     

Changes in (markers of) bone metabolism during high dose corticosteroid pulse treatment in patients with rheumatoid arthritis.

OBJECTIVE: To examine the effect of high dose corticosteroid pulse treatment (three times 200 mg dexamethasone intravenously in eight days) on calcium and bone metabolism in 17 consecutive patients with active rheumatoid arthritis (RA). METHODS: Bone formation was quantified by measurement of serum alkaline phosphatase, osteocalcin, and carboxyterminal propeptide of type I procollagen (pro-I-CPP) concentrations. Bone resorption was measured by urinary excretion of calcium, hydroxyproline, (free and total) deoxypyridinoline (Dpyr), (free and total) pyridinoline (Pyr), and serum concentrations of the carboxyterminal cross linked telopeptide of type I collagen (I-CTP). Disease activity of RA was measured by erythrocyte sedimentation rate, C reactive protein, and Ritchie and Thompson joint scores. RESULTS: Disease activity was initially high, and decreased during corticosteroid pulse treatment and the following five weeks. Osteocalcin, alkaline phosphatase, and pro-I-CPP concentrations were initially within normal limits, while I-CTP, Dpyr, and Pyr were increased. Osteocalcin and pro-I-CPP concentrations decreased (p < 0.01) during corticosteroid pulse treatment, but rapidly returned to baseline after the treatment. No changes were observed in alkaline phosphatase and urinary excretion of calcium and hydroxyproline. Bone resorption measured by serum I-CTP and urinary excretion of Pyr and Dpyr was unchanged or decreased (p < 0.05-0.01), depending on the time of measurement and the parameter measured. CONCLUSIONS: In these patients with active RA, bone resorption was increased, while bone formation was within normal limits. During high dose corticosteroid pulse treatment, bone formation was only transiently decreased, while markers of bone resorption were unchanged or decreased. Because corticosteroid pulse treatment has only a short term negative effect on bone formation, and because it probably reduces bone resorption, at least partly as a result of the decreased disease activity, the effect of corticosteroid pulse treatment on bone may be assumed to be relatively mild.