Prevention and treatment of osteopenia in the ovariectomized rat: Effect of combined therapy with estrogens, 1-alpha vitamin D, and prednisolone

Geusens, Piet; Dequeker, Jan; Nijs, J; Verstraeten, A; Bramm, E.

doi:10.1007/bf02555877

Cited by 23 publications

(12 citation statements)

References 33 publications

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“…In ovariectomized and corticosteroid-treated rats, alfacalcidol had a strong preventive and curative effect on bone mass and mechanical strength [10,11]. Sambrook et al [12] investigated the preventive effect on bone loss of calcitonin, calcitriol and calcium as compared with calcitriol plus calcium or calcium alone in patients receiving 25 mg prednisolone per day as a starting dose tapered to a mean daily dose of 13.5 mg.…”

Section: Discussionmentioning

confidence: 98%

Prophylactic Use of Alfacalcidol in Corticosteroid-Induced Osteoporosis

Reginster

Kuntz

Verdickt

et al. 1999

Osteoporosis International

107

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One hundred and forty-five patients suffering from diseases requiring long-term treatment with high doses of corticosteroids (30 mg/day or greater of prednisolone) were recruited to the study. Patients had to be steroid naive on entry to the study (not more than 15 days of treatment with a corticosteroid within the previous 24 months). Patients were randomized to receive either 1 microgram/day alfacalcidol or placebo capsules for 12 months. Bone mineral density (BMD) of the lumbar spine was assessed by dual-photon absorptiometry on entry and after 3, 6 and 12 months' treatment. Safety was monitored by the recording of all adverse events reported by patients and the regular screening of blood samples for hematology and serum biochemistry. Of the 145 patients, 74 were randomized to alfacalcidol and 71 to placebo. The treatment groups were well matched at baseline with no significant differences in demographic, clinical or biochemical parameters. The mean equivalent dose of prednisolone at baseline was 46.6 mg/day and 46.3 mg/day for the alfacalcidol and placebo group respectively. From the 145 patients randomized to treatment, 71 (38 who received alfacalcidol and 33 who received placebo) provided BMD data both at baseline and at 3, 6 and 12 months. The percentage change in BMD after 6 months' treatment was -2.11% in the alfacalcidol group and -4.00% in the placebo group (p = 0.39). After 12 months the percentage change in BMD was +0.39% (CI: -4.28 to 4.81) in the alfacalcidol group and -5.67% (CI: -8.13 to -3.21) in the placebo group, this difference (6.06%, CI: 0.88 to 11.24) being statistically significant (p = 0.02). An intention to treat analysis also showed a significant difference between the two treatment groups in alfacalcidol's favor (3.81%, p = 0.01; CI: 0.92 to 6.70). There was no significant difference between the two treatment groups in the corticosteroid dose at any time point during the study. Serum calcium was measured throughout and there were no significant differences between the two treatment groups at any visit. This study suggests that alfacalcidol can prevent corticosteroid-induced bone loss from the lumbar spine. Long-term use of alfacalcidol was not associated with any significant adverse effects in this diverse group of patients.

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Section: Discussionmentioning

confidence: 98%

Prophylactic Use of Alfacalcidol in Corticosteroid-Induced Osteoporosis

Reginster

Kuntz

Verdickt

et al. 1999

Osteoporosis International

107

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“…In growing rats, treatment with alphacalcidol resulted in a consistant increase in biomechanical competence of the bone, accompanied by a significant decrease in insulin-like growth factor I concentration in the bone matrix [23]. In young overiectomized rats treated with prednisone, alphacalcidol significantly increased bone mass, both in males and in females [24]. Besides increasing intestinal absorption and reducing bone resorption in prednisone-treated intact rats, a synthetic hormone analog (ED-71) was also shown to induce a dosedependent increase in trabecular bone volume of the lumbar spine [3,25].…”

Section: Vitamin D D-hormones and Pathogenesis Of Glucocorticoid-inmentioning

confidence: 95%

Alphacalcidol in Prevention of Glucocorticoid-Induced Osteoporosis

Reginster¹,

Froidmont²,

Lecart

et al. 1999

Calcif Tissue Int

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One of the major drawbacks of glucocorticoids long-term therapy is the occurrence of a severe osteoporosis characterized by fractures occurring at different sites, mainly at the level of trabecular bone. One of the major determinants of glucocorticoid-induced osteoporosis is a decrease in the intestinal absorption of calcium (Ca) leading to a secondary hyperparathyroidism. D-hormones have been shown to significantly improve Ca absorption in the gut and subsequently to decrease parathyroid hormone circulating levels, hence normalizing bone turnover. In a recent study evaluating 145 patients suffering from diseases requiring long-term treatment with high doses of corticosteroids, we have demonstrated a significant benefit of alphacalcidol (1 microg/day) over placebo in terms of changes in bone mineral density of the lumbar spine. These results are in accordance with studies showing better prevention of bone loss and vertebral fractures in cardiac transplant patients treated with alphacalcidol than those treated with etidronate. There is now a convergent body of evidence to suggest that alphacalcidol is a reasonable, safe, and effective option for the prevention of glucocorticoid-induced osteoporosis, provided that serum Ca is monitored on a regular basis.

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“…This effect probably was mediated through stimulation of periosteal bone apposition. Earlier studies using radiogrammetry or histological analysis also have suggested positive effects of vitamin D metabolites on cortical bone in rats (45,46) …”

Section: Discussionmentioning

confidence: 98%