25-Hydroxycholecalciferol as an antagonist of adverse corticosteroid effects on phosphate and calcium metabolism in man

The present study was performed in 30 patients who needed steroid therapy: courses of triamcinolone or DTM 8-15 given orally lasted 30 days. In 15 of these patients glucoactive corticosteroids were administered in combination with 5 micrograms/day of 25OH-vitamin D3 (25OHD3). 47Calcium oral test and 99mTc-MDP kinetics, as an index of bone turnover, were performed at the beginning of the therapy and after 30 days. At the end of treatment a significant improvement of intestinal radiocalcium transport together with a decrease in bone turnover in the group of patients treated with 25OHD3 was observed. As it concerns plasma calcium level, inorganic phosphate, the urinary excretion of calcium, phosphate and hydroxyproline no significant difference between the two groups examined were noticed. These results indicate that the adverse effects of glucoactive corticosteroids on intestinal calcium transport and bone turnover may be counteracted by the combined administration of physiological doses of 25OHD3.     

The effect of a gonadotropin-releasing hormone agonist analog (nafarelin) on bone metabolism

The effect on bone metabolism of an agonist analog of GnRH, nafarelin, was studied in 16 premenopausal women, who received 200 micrograms nafarelin/day for 6 months, and 9 premenopausal women, who received 400 micrograms nafarelin/day for 6 months, followed by a 6-month follow-up period. Bone mineral content in the forearm (measured by single photon absorptiometry) and in the spine (measured by dual photon absorptiometry) significantly decreased after 6 months of treatment with 400 micrograms nafarelin, but 6 months after termination of treatment all bone mineral measurements had returned to pretreatment levels. The bone mineral measurements in the 200 micrograms group did not change throughout the study. In both treatment groups the biochemical estimates of bone turnover increased significantly to postmenopausal levels. Withdrawal of treatment resulted in an abrupt decrease in the bone resorption parameters (fasting urinary hydroxyproline to creatinine and calcium to creatinine excretion ratios and serum phosphate), whereas there was a protracted fall in the bone formation parameters (plasma bone Gla protein and serum alkaline phosphatase) 6 months after termination of treatment. Our findings demonstrate that nafarelin in both doses increased biochemical indices of bone turnover, that 400 micrograms/day nafarelin resulted in a significant decrease in bone mineral content, and that these effects were reversible.     

Bone metabolism during methylprednisolone pulse therapy in rheumatoid arthritis.

The deleterious effects of corticosteroids (CS) on bone are well known, but probably differ depending on duration and dosage of CS therapy. Presently huge amounts of CS are given over a short period of time in different rheumatic conditions. Not much is known about the effect of this kind of CS treatment on bone metabolism. Twenty patients with persistently active rheumatoid arthritis were treated with 1 g methylprednisolone (MP) three times on alternate days over a five day period. Twenty four hours after the first MP pulse serum calcium was increased and the values of parathyroid hormone and 1,25-dihydroxyvitamin D tended to increase. After the second MP pulse, however, these values had returned to the starting values. The urinary calcium excretion increased during MP pulse therapy and returned to the initial value immediately after the pulse therapy. The hydroxyproline excretion tended to decrease during therapy and stayed decreased immediately afterwards, indicating a decrease in bone resorption. It is concluded that bone metabolism is not seriously affected during MP pulse therapy.     

Osteogenesis imperfecta types I,III, and IV: effect of pamidronate therapy on bone and mineral metabolism

Cyclical iv therapy with pamidronate improves the clinical course in children and adolescents with osteogenesis imperfecta (OI). In this study we evaluated the effect of this therapy on bone and mineral metabolism in 165 patients with OI types I, III, and IV (age, 2 wk to 17.9 yr; 86 girls and 79 boys). All patients received iv pamidronate infusions on 3 successive days, administered at age-dependent intervals of 2-4 months. During the 3 d of the first infusion cycle, serum concentrations of ionized calcium dropped by 0.14 +/- 0.008 mmol (mean +/- SE; P < 0.001), and serum PTH levels transiently almost doubled (P < 0.001). At the same time, urinary excretion of the bone resorption marker type I collagen N-telopeptide related to creatinine (uNTX/uCr) decreased by 61-73% (P < 0.001). Two to 4 months later, ionized calcium had returned to pretreatment levels, and uNTX/uCr remained 30-35% lower than at baseline (P < 0.001). During 4 yr of pamidronate therapy (n = 40 patients), ionized calcium levels remained stable, but PTH levels increased by about 30% (P < 0.01). uNTX/uCr, expressed as a percentage of the age- and sex-specific mean value in healthy children, decreased from 132 +/- 13% (mean +/- SE) at baseline to 49 +/- 3% after 4 yr of therapy (P < 0.001). In conclusion, serum calcium levels can decrease considerably during and after pamidronate infusions, requiring close monitoring especially at the first infusion cycle. In long-term therapy, bone turnover is suppressed to levels lower than those in healthy children. The consequences of chronically low bone turnover in children with OI are unknown at present.     

Long-term treatment of acromegaly with lanreotide: evidence of increased serum parathormone concentration

The somatostatin analogue lanreotide is effective in reducing growth hormone levels in patients with acromegaly. Acromegaly is characterized by calcium homeostasis alterations. The aim of our study was to evaluate the effects of lanreotide on bone turnover markers in a group of acromegalic patients and to verify a possible increase of intact parathormone (iPTH) levels in a transient or persistent way. Serum GH, IGF-I and serum and urinary markers of bone metabolism were measured before treatment and on months 3 and 24. In short-term treatment (3 months), lanreotide significantly decreased GH, IGF-I, serum calcium, osteocalcin and alkaline phosphatase levels, but increased iPTH level (49 +/- 16.7 vs pre-treatment 28.3 +/- 7.6 ng/L, p<0.001). During long-term study (24 months) GH and IGF-I were significantly still low; serum calcium and alkaline phosphatase levels returned to pre-treatment levels. iPTH level was significantly still higher compared with pre-treatment (46.4 +/- 9.2 vs 28.3 +/- 7.6 ng/L, p<0.05). No changes were seen in serum albumin, creatinine and vitamin D during short and long term treatment. The changes of most bone markers during lanreotide treatment can be explained by the decrease of GH and IGF-I. The increase of iPTH concentration suggests that lanreotide has ulterior and long-standing actions on calcium homeostasis: intestinal malabsorption of calcium due to the lanreotide could contribute to this "secondary" hyperparathyroidism. The clinical relevance of these long-standing effects needs to be further investigated.     

Paget''s disease of bone treated with a five day course of oral tiludronate.

Chloro-4-phenyl thiomethylene bisphosphonate (tiludronate) is a new drug which can be used as an inhibitor of bone resorption. As it remains in bone for a long time, and as mineralisation defects have only been seen at doses much higher than those required to decrease osteoclastic activity, it could be given at high doses over a short period of time. Eighteen patients with Paget's disease of bone were randomly allocated to three therapeutic groups receiving respectively 600, 800, and 1200 mg/day tiludronate for five days. Serum alkaline phosphatase activity and the urinary hydroxyproline/creatinine ratio were quickly and drastically reduced in all three groups. A significant reduction of serum alkaline phosphatases and the hydroxyproline/creatinine ratio was still present six months after the five day therapeutic course, reflecting a sustained activity of tiludronate even after stopping treatment. Dose dependent short and long term reductions of bone turnover rate were observed. Biochemical assessment of haematological, renal, or hepatic tolerance did not show any toxicity of tiludronate. Fifty per cent of patients treated by a dose of 1200 mg/day reported gastrointestinal disturbances, however, making this dosage unsuitable for clinical practice.     

Effect of bisphosphonate therapy and parathyroidectomy on the urinary excretion of galactosylhydroxylysine in primary hyperparathyroidism

BACKGROUND In patients with mild or asymptomatic primary hyperparathyroidism a reliable index of bone resorption might be useful for appropriate management. Hydroxyproline is the most commonly used marker of bone resorption but its low specificity and sensitivity are known. Galactosylhydroxylysine, an aminoacid mainly represented in bone collagen, has been proposed as a more suitable index of bone resorption. In this study we evaluated the sensitivity of galactosylhydroxylysine and hydroxyproline assays in following the changes of their urinary levels in 12 patients with mild primary hyperparathyroidism before and after treatment with bisphosphonate and surgery. METHODS Serum and fasting urine specimens were obtained from 12 women with mild primary hyperparathyroidism before and after bisphosphonate treatment (2.5 mg daily for 5 days, intravenously) and after a further 25 days; in 7 patients biochemical tests were also performed 1 and 6 days after parathyroidectomy. Galactosylhydroxylysine was assayed by an HPLC method and hydroxyproline by a RIA commercial kit. RESULTS Baseline galactosylhydroxylysine urinary levels were far above the normal range in all the patients whilst in 8 of them baseline hydroxyproline levels were normal. Bisphosphonate treatment significantly decreased bone turnover as shown by a significant fall in serum calcium (from 2.9 to 2.6 mmol/l; P < 0.001) and in galactosylhydroxylysine and hydroxyproline (?55 and ?31% respectively). Twenty-five days after the end of treatment, resorption increased again and serum calcium and galactosylhydroxylysine, but not hydroxyproline, rose significantly towards basal levels. One day after parathyroidectomy serum calcium, galactosylhydroxylysine and PTH showed reduction below normal ranges. PTH and galactosylhydroxylysine returned to normal values at day 6 after parathyroidectomy. No changes in hydroxyproline levels were seen. Galactosylhydroxylysine, but not hydroxyproline, correlated significantly with serum calcium and PTH. CONCLUSION Galactosylhydroxylysine appears to be a sensitive index of bone resorption, useful in the clinical assessment of bone involvement and in the management of patients with mild primary hyperparathyroidism.     

Therapy of hypercalcemia due to parathyroid carcinoma with intravenous dichloromethylene diphosphonate

Dichloromethylene diphosphonate (Cl2MDP) a potent inhibitor of osteoclast-mediated bone resorption, lowers serum calcium in hypercalcemia associated wit malignancies and with primary hyperparathyroidism, and reduces excess calcium mobilization from bone in multiple myeloma and in Paget's disease. We have evaluated the effectiveness of intravenously administered Cl2MDP in five patients with parathyroid carcinoma, a disorder characterized by severe hypercalcemia, very high parathyroid hormone (PTH) levels, and marked osteoclast-mediated bone resorption. All patients had biopsy-proved metastatic parathyroid carcinoma and hypercalcemia which persisted after multiple surgical procedures and other attempts at management. During a three-day observation period, each patients continued to demonstrate stable or progressive hypercalcemia despite infusion with saline solution and furosemide. Cl2MDP was administered over 2 hours at 2.5 mg/kg on day 1 and 5 mg/kg on days 2 through 7. Response was noted in all five patients; there was a gradual decline in the average serum calcium from 16.0 +/- 1.1 mg/dl (SEM) to 11.1 +/- 0.9 mg/dl by the eighth day (p less than 0.01). There were concomitant reductions in urinary calcium excretion, from 798 +/- 153 mg/g creatinine to 350 +/- 96 mg/g creatinine (p less than 0.05) and in the urinary hydroxyproline excretion, from 155 +/- 38 mg/g creatinine to 94 +/- 29 mg/g creatinine (p less than 0.02). Serum PTH levels remained markedly elevated (460 +/- 141 micrograms eq/ml to 493 +/- 169 micrograms eq/ml). In three patients, all indices returned to pretreatment levels by 10 days after the last infusion. In two of these patients there was a response to retreatment with Cl2MDP with a fall in calcium from 16.9 +/- 0.5 mg/dl to 12.4 +/- 1.5 mg/dl. There was no response in one patient. No adverse reactions to Cl2MDP were observed. The decrease in serum calcium and concomitant declines in urinary calcium and hydroxyproline suggest that Cl2MDP can effectively inhibit the excessive bone resorption associated with parathyroid carcinoma.     

Evaluation of bone metabolism after the use of an inhaled glucocorticoid (flunisolide) in patients with moderate asthma

OBJECTIVE: We have investigated the effects of the inhaled corticosteroid flunisolide on bone metabolism and adrenal function in patients with moderate asthma. SUBJECTS AND DESIGN: Twenty ambulatory patients (13 females, 7 males, mean age +/- SD of 36.4 +/- 12.4 years) with moderate asthma were recruited. None had taken corticosteroids for at least 1 month. Flunisolide 500 microg was given twice a day for 10 weeks, without any other medication. Blood and urine were collected before and at the end of treatment course. Cortisol (basal and 1 h after ACTH 250 microg i.v.) was measured to evaluate adrenal function. A peak cortisol response of 496 nmol/l was considered an adequate response. Serum ionized calcium, intact PTH, plasma osteocalcin (OC) and urinary pyridinoline (Pyr) and deoxy-pyridinoline (D-Pyr) were measured to evaluate bone metabolism. Wilcoxon paired test was performed for statistical analysis. Results are expressed as mean +/- SD. RESULTS: In most patients (85%), there was no difference after treatment with flunisolide on basal and stimulated cortisol levels. We found a significant decrease of OC (3.55 +/- 1.42 to 2.97 +/- 1.05 nmol/l) and Pyr (66.4 +/- 20.0 to 59.5 +/- 24.9 pmol/micromol creatinine) levels after treatment (P < 0.05). We also observed a positive correlation between the variations seen in pre and post treatment values of OC and Pyr/D-Pyr. CONCLUSIONS: The use of inhaled flunisolide 1000 microg/day for 10 weeks had no suppressive effect on adrenal function in the majority of asthmatic patients studied. However, the effects seen on bone and mineral metabolism, evidenced by the significant fall in osteocalcin and pyridinoline levels, may indicate a possible systemic effect of this drug. Clinical consequences of long-term treatment with flunisolide need to be further evaluated.     

Effects of estrogens and calcium on calcitonin secretion in postmenopausal women

The protective action of estrogens on bone mass may be mediated by an increase in calcitonin (CT) secretion. We reevaluated this hypothesis using a method for measuring CT in extracts of serum that allows sensitive specific measurement of CT monomer. We studied seven healthy postmenopausal women before and on the 7th and 28th days of each of three 4-week treatment periods: estrogen (estradiol valerate; 2 mg/day), calcium supplement (1500 mg/day), and estrogen plus calcium; the three cycles were separated by intervals of 4 weeks. Serum extractable CT (exCT) levels were measured before and after a short calcium stimulation test (2 mg Ca/kg in 5 min) to assess the C-cell secretory response on each day. Estrogen had the expected biological effects, decreasing (P less than 0.05) serum gonadotropin concentrations and fasting or 24-h urinary calcium excretion. The calcium supplement caused a significant increase in 24-h urinary calcium excretion. However, there was no increase in basal or stimulated serum exCT levels during any of the three cycles. On the contrary, basal serum exCT concentrations decreased slightly but significantly during estrogen treatment from 1.9 +/- 0.5 (+/- SE) to 1.5 +/- 0.4 ng/L on day 7 and 1.2 +/- 0.2 ng/L on day 28 (P less than 0.05). This decrease in basal exCT levels did not occur during the combined estrogen and calcium administration period, probably because the slight decrease in serum calcium induced by estrogen did not occur during combined estrogen and calcium administration. In summary, estrogens do not stimulate CT secretion; variations in serum exCT levels appear to be related to the changes in bone metabolism induced by estrogens.     

Deconditioning increases bone resorption and decreases bone formation in the rat

The response of calcium metabolism and bone turnover to deconditioning after exercise training was studied in three groups of Sprague-Dawley female rats: age-matched controls, 12-week treadmill training, and 8-week treadmill training followed by 4-week discontinuation of training. The exercised rats had a higher absorption efficiency of calcium that decreased to control levels as early as 2 weeks following discontinuation of training. Urinary calcium excretion increased by 2 weeks of deconditioning and then reverted to control levels; bone mineral content measurements declined following deconditioning. Tracer uptake of 45Ca in the femur demonstrated an increase in bone formation that was present during exercise, but was not evident following 4 weeks of deconditioning. The urinary excretion of prelabeled 3H-tetracycline was used to investigate bone resorption in two groups of exercised rats; one group continued to exercise and in the other group the exercise was discontinued. Bone resorption increased within 4 to 11 days after deconditioning and returned to basal levels by the 10th day, at which time the net bone retention of 3H-tetracycline was 86% of that of the group that continued exercising. We conclude that exercise must be continued to sustain any gain it produces in bone mineral. Bone mass gained through exercise will be lost during deconditioning as a result of a decline in bone formation and an increase in bone resorption.     

Gallium nitrate in prostatic cancer: evaluation of antitumor activity and effects on bone turnover

Gallium nitrate, an agent known to inhibit bone resorption, was evaluated in patients with bidimensionally measurable hormone-refractory prostatic cancer. The starting dose was 200 mg/m2 iv by continuous infusion over 7 days. Two patients (10%; 95% confidence limits, 0%-22%) achieved short partial remissions of 1 and 6+ months, while seven of 23 (30%; 95% confidence limits, 14%-52%) showed a diminution of bone pain. Serial indices of bone turnover including serum calcium, phosphorus, and urinary hydroxyproline excretion showed a significant decrease at the completion of the infusion which returned to baseline prior to the next cycle. The data suggest the effect on bone was too short to produce consistent improvement. Reasons for the dissociation of pain relief and antitumor activity are discussed.     

Effects of different regimes of corticosteroid treatment on calcium and bone metabolism in rheumatoid arthritis

Summary A clinical study of 30 patients with rheumatoid arthritis was undertaken in order to assess the acute effects of corticosteroids on calcium and bone metabolism. The patients were randomly divided into 3 groups. The first group was not treated with corticosteroids, the second group was treated with 3 oral pulses of 100 mg prednisolone and the third group received 3 intravenous pulses of 1000 mg methylprednisolone (MP) on alternate days during one week. In both steroid treated groups the serum parathyroid hormone concentration tended to increase. In the MP treated group an increase in the 1.25-dihydroxyvitamin D concentration after the first pulse was followed by a significant drop; this effect was also seen, but somewhat retarded and less distinct, in the orally treated group. In the MP treated group the urinary calcium excretion raised significantly 6 hrs after the first pulse and then dropped significantly. In all groups no changes were found in the serum calcium level and the urinary excretion of hydroxyproline. We conclude that, acute changes in calcium and bone metabolism occur during treatment with intravenous pulses of methylprednisolone and with oral pulses of prednisolone. These changes are small and reversible in a few days.     

The systemic effect of intraarticular administration of corticosteroid on markers of bone formation and bone resorption in patients with rheumatoid arthritis

Objective. To assess the effects of intraarticular (IA) corticosteroid use on bone metabolism in patients with rheumatoid arthritis (RA). Methods. Levels of the bone turnover markers, serum osteocalcin (BGP) and urinary pyridinoline (PYD), were monitored in RA patients for 4 weeks following a single IA administration of xylocaine alone or in combination with triamcinolone acetonide. Results. Levels of the bone resorption marker, PYD, did not show any significant change, whereas BGP levels were drastically decreased 1 day after IA administration of corticosteroid, and then returned to pretreatment levels by day 14. The efficacy of IA corticosteroid treatment lasted for 4 weeks. Conclusion. Our results suggest that IA administration of corticosteroid has no net effects on bone resorption and only a transient systemic effect on bone formation. IA corticosteroid administration may be better for bone metabolism than continuous use of orally administered corticosteroid.     

Bone and calcium metabolism in subclinical autoimmune hyperthyroidism and hypothyroidism

Bone turnover is reported to increase in favour of resorption in overt hyperthyroidism and the rate of resorption is associated with the levels of thyroid hormones. Hypothyroidism, on the other hand, was shown to cause no disturbance of calcium kinetics and found to associate lower trabecular resorption surfaces and increased bone cortical thickness. Similar studies are very rare in subclinical thyroid disorders and consequently we aimed to examine calcium and bone metabolism in subclinical thyroid disorders. Thirteen patients with subclinical hyperthyroidism secondary to untreated Graves' disease, 20 patients with subclinical hypothyroidism and 10 healthy subjects participated in this survey. Briefly calcium, phosphorus, and creatinine (Cre), urinary deoxypyridinoline (U-DPD) and serum osteocalcin (OC) were measured as biochemical markers for calcium metabolism. Concerning serum Ca and phosphorus levels, there were no differences between three of the groups, but urinary Ca excretion was higher in subclinical hyperthyroid patients compared to control and hypothyroid subjects. Hypothyroid patients had similar U-DPD levels with control subjects (p = 0.218). Serum OC and U-DPD were higher in subclinical hyperthyroid compared to control subjects (p<0.001 and p<0.001 respectively). We demonstrated a higher bone turnover and greater calcium excretion in subclinical hyperthyroid patients. Additionally, we found that subclinical hypothyroidism is not associated with disturbed calcium metabolism. As persistent increase in bone turnover is responsible for accelerated bone loss, patients with Graves' disease may have increased risk for osteoporosis.     

Changes in calcium and bone metabolism during treatment with low dose prednisone in young,healthy, male volunteers

Summary The effect of low dose prednisone on calcium and bone metabolism was evaluated in 8 healthy, young, male volunteers. Sodium and calcium intake were kept stable during the whole study period of 7 weeks. Week 0 was the baseline period; during week 1, 3 and 5 prednisone (10 mg/day) was given, during week 3 together with 500 mg elementary calcium and during week 5 with 4000 IU vitamin D on alternate days. During week 2, 4 and 6 no medication was given. No changes occurred in fasting urinary excretion of calcium or hydroxyproline, nor in serum levels of alkaline phosphatase, 25-Vitamin D, PTH, creatinine and inorganic phosphorus. A rapid decrease of serum osteocalcin during prednisone intake was found (p<0.01). This dip also occurred during prednisone and vitamin D treatment, but did not occur when calcium was added to prednisone, although the baseline value was lower at the start of combined treatment with prednisone and calcium. Serum calcium decreased during prednisone (p<0.05), but when prednisone was given together with calcium, an increase of serum calcium was found. (p<0.05).It is concluded that 10 mg prednisone/day decreases bone formation, as shown by its effect on osteocalcin, while no influence is seen on bone resorption. Thus, prednisone, even when used in low doses, influences bone metabolism by uncoupling bone formation (decreased) and bone resorption (unchanged). These data suggest that the Cs-associated decrease in serum osteocalcin and in serum calcium does not occur during calcium suppletion.     

Prevention of bone loss by hormone replacement therapy is probably not due to stimulation of calcitonin secretion

Weekly fasting serum calcitonin levels and biochemical indices of bone metabolism were measured in 13 postmenopausal women being given hormone replacement therapy over a period of 8 weeks. All of the biochemical indices except urinary hydroxyproline creatinine ratios fell significantly, indicating that the treatments were effective in reducing bone turnover. Calcitonin levels fell significantly and, within the individual, levels were positively correlated with adjusted calcium levels. These findings do not support the theory that estrogen conserves bone by stimulating calcitonin secretion.     

Calcium supplementation reduces vertebral bone loss in perimenopausal women: a controlled trial in 248 women between 46 and 55 years of age

To study the effect of calcium supplementation on perimenopausal bone loss, 295 women were randomized into a control group and 2 supplementation groups receiving, respectively, 1000 and 2000 mg elemental calcium/day for a period of 2 yr. We observed a significant decrease in lumbar bone loss in relation to the calcium supplementation (mean loss after 2 yr of 3.5% in the control group vs. 1.3% and 0.7% in the 1000 and 2000 mg groups, respectively), a significant increase in urinary calcium excretion, and a significant decrease in the urinary hydroxyproline/creatine ratio, serum alkaline phosphatase, osteocalcin, and 1,25-dihydroxyvitamin D. The effect of calcium supplementation on lumbar bone loss was significant in the first year of supplementation, but not in the second. However, the urinary hydroxyproline/creatinine ratio and the serum alkaline phosphatase level remained significantly decreased in the treatment groups at the end of the study; this was not the case for serum osteocalcin. Calcium supplementation did not have a significant effect on metacarpal cortical bone loss. The difference in biochemical parameters between the 2 supplementation groups was small. No significant interaction was observed between the menopausal status of the subjects and the effect of calcium supplementation. We conclude that calcium supplementation retards lumbar bone loss in the first year of calcium supplementation by reducing bone turnover. However, the effect on lumbar bone loss over a longer time span is still uncertain.     

The effects of triiodothyronine on bone metabolism in healthy ambulatory men.

The purpose of the present study was to determine the effects of supraphysiologic doses of triiodothyronine (T(3)) on skeletal metabolism, calcium balance, and the calciotropic hormones. Seven healthy, lean men were studied in an inpatient metabolic unit over a 63-day period. All volunteers received oral T(3) at doses of 50-75 microg/d. There was a prompt and sustained increase in calciuria and an overall net negative calcium balance. The pattern of changes in serum osteocalcin, urinary deoxypyridinoline (DPD)/creatinine ratio, and serum bone-specific alkaline phosphatase indicated an early increase in bone resorption followed by a late, incomplete compensatory increase in bone formation. Cumulative net calcium loss was 18.5 +/- 5.4 g over the 63-day treatment period, averaging 218.5 +/- 41.4 mg/d. This represents 0.22% +/- 0.075% of the total skeletal calcium content. The cumulative net calcium loss over the 63-day treatment period was highly correlated with the change in DPD (r = -0.95, p = 0.001). Prompt increases in corrected serum calcium values resulted in serum intact parathyroid hormone (iPTH) levels decreasing by 30.4% (p = 0.08). Bone mineral density showed no change. We conclude that T(3) accelerates bone turnover and that bone formation does not increase acutely to prevent bone loss.     

Weaning triggers a decrease in receptor activator of nuclear factor-kappaB ligand expression, widespread osteoclast apoptosis, and rapid recovery of bone mass after lactation in mice

A significant portion of milk calcium comes from the mother's skeleton, and lactation is characterized by rapid bone loss. The most remarkable aspect of this bone loss is its complete reversibility, and the time after weaning is the most rapid period of skeletal anabolism in adults. Despite this, little is known of the mechanisms by which the skeleton repairs itself after lactation. We examined changes in bone and calcium metabolism defining the transition from bone loss to bone recovery at weaning in mice. Bone mass decreases during lactation and recovers rapidly after weaning. Lactation causes changes in bone microarchitecture, including thinning and perforation of trabecular plates that are quickly repaired after weaning. Weaning causes a rapid decline in urinary C-telopeptide levels and stimulates an increase in circulating levels of osteocalcin. Bone histomorphometry documented a significant reduction in the numbers of osteoclasts on d 3 after weaning caused by a coordinated wave of osteoclast apoptosis beginning 48 h after pup removal. In contrast, osteoblast numbers and bone formation rates, which are elevated during lactation, remain so 3 d after weaning. The cessation of lactation stimulates an increase in circulating calcium levels and a reciprocal decrease in PTH levels. Finally, weaning is associated with a decrease in levels of receptor activator of nuclear factor-kappaB ligand mRNA in bone. In conclusion, during lactation, bone turnover is elevated, and bone loss is rapid. Weaning causes selective apoptosis of osteoclasts halting bone resorption. The sudden shift in bone turnover favoring bone formation subsequently contributes to the rapid recovery of bone mass.