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01-04-2004 | Original Article

Efficacy of alphacalcidol and calcitriol in primary and corticosteroid-induced osteoporosis: a meta-analysis of their effects on bone mineral density and fracture rate

Authors: Florent Richy, Olivier Ethgen, Olivier Bruyere, Jean-Yves Reginster

Published in: Osteoporosis International | Issue 4/2004

Abstract

Vitamin D metabolites alphacalcidol and calcitriol (D-hormones) have been investigated for two decades, but few and conflicting results are available from high-quality randomized controlled trials. Our objectives were to provide an evidence-based update quantitatively summarizing their efficacy on bone mineral density (BMD) and fracture rate. We performed a systematic research of any randomized controlled trial containing relevant data, peer review, data extraction and quality scoring blinded for authors and data sources, and comprehensive meta-analyses of the relevant data. Inclusion criteria were: randomized controlled study, calcitriol or alphacalcidol, BMD or fractures in healthy/osteopenic/osteoporotic patients exposed or not to corticosteroids (CS). Analyses were performed in a conservative fashion using professional dedicated softwares and stratified by outcome, target patients, study quality, and control-group type. Results were expressed as effect size (ES) for bone loss or relative risk (RR) for fracture while allocated to D-hormones vs control. Publication bias and robustness were investigated. Of the trials that were retrieved and subsequently reviewed, 17 papers fitted the inclusion criteria and were assessed. Quality scores ranged from 20 to 100%, the mean (standard deviation) being 72 (22)%. Calcitriol and alphacalcidol were found to have the same efficacy on all outcomes at p>0.13. We globally assessed D-hormones effects in preventing bone loss in patients not exposed to CS, and found positive effect: ES=0.39 (p<0.001). For lumbar spine, this particular effect was 0.43 (p<0.001). D-hormones significantly reduced the overall fracture rates: RR=0.52 (0.46; 0.59) and both vertebral and non-vertebral fractures: RR=0.53 (0.47; 0.60) and RR=0.34 (0.16; 0.71), respectively. No statistical difference in response was observed between results from studies on healthy and osteoporotic patients or depending on the fact that controls were allowed to calcium supplementation. Treatment with D-hormones was evaluated for maintaining spinal bone mass in five trials of patients with CS-induced osteoporosis, and provided ES=0.43 at p<0.001. Only two studies specifically addressed the effects of calcitriol on spinal fracture rate. None of them provided significant results, and the global RR did not reach the significance level as well: RR=0.33 (0.07; 1.51). Our data demonstrated efficacy for DH on bone loss and fracture prevention in patients not exposed to CS and on bone loss in patients exposed to CS, in the light of the most reliable scientific evidence. Their efficacy in reducing the number of fractures in patients exposed to CS remains to be determined.

Tosteson AN, Gabriel SE, Grove MR, Moncur MM, Kneeland TS, Melton (2001) Impact of hip and vertebral fractures on quality-adjusted life years. Osteoporos Int 12:1042–1049CrossRefPubMed

Adachi JD, Loannidis G, Berger C, Jospeh L, Papaioannou A, Pickard A et al. (2001) The influence of osteoporotic fractures on health-related quality of life in community-dwelling men and women across Canada. Osteoporos Int 12:903–908CrossRefPubMed

Silverman SL, Minshall ME, Shen W, Harper KD, Xie S (2001) The relationship of health-related quality of life to prevalent and incident vertebral fracture in postmenopausal women with osteoporosis: results from the Multiple Outcomes of Raloxifene Evaluation Study. Arthritis Rheum 44:2611–2619CrossRefPubMed

Gold DT (2001) The nonskeletal consequences of osteoporotic fractures: psychologic and social outcomes. Rheum Dis Clin N Am 27:255–262

Maratolli RA, Berkman LF, Cooney LM (1992) Decline in physical function following hip fracture. J Am Geriatr Soc 40:861–866

Osteoporosis prevention, diagnosis, and therapy (2000) NIH consensus statement, no. 17, pp 1–36

Richy F, Bousquet J, Ehrlich G, Meunier P, Israel E, Morii H et al. (2003) Inhaled corticosteroids effects on bone in asthmatic and COPD patients: a quantitative systematic review. Osteoporos Int 14:179–190PubMed

Baylink DJ (1983) Glucocorticoid-induced osteoporosis. N Engl J Med 309:306–308PubMed

Seeman LV (1982) Differential effects of endocrine dysfunction on the axial and the appendicular skeleton. J Clin Invest 69:1302–1309PubMed

10.

Avioli LV (1984) Effects of chronic corticosteroid therapy on mineral metabolism and calcium absorption. Adv Exp Med Biol 171:81–89PubMed

11.

Adinoff AD, Hollister JR (1983) Steroid-induced fractures and bone loss in patients with asthma. N Engl J Med 309:265–268PubMed

12.

Meunier PJ, Dempster DW, Edouard C, Chapuy MC, Arlot M, Charhon S (1984) Bone histomorphometry in corticosteroid-induced osteoporosis in Cushing’s syndrome. Adv Exp Med Biol 171:191–200PubMed

13.

Black DM, Cummings SR, Karpf DB, Cauley JA, Thompson DE, Nevitt MC et al. (1996) Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Fracture Intervention Trial Research Group. Lancet 348:1535–1541PubMed

14.

Cummings S, Black D, Thompson D, Applegate W, Barrett-Connor E, Musliner T et al. (1998) Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the Fracture Intervention Trial. J Am Med Assoc 280:2077–2082CrossRef

15.

Ettinger B, Black D, Mitlak B, Knickerbocker R, Nickelsen T, Genant H et al. (1999) Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. Multiple outcomes of raloxifene evaluation (MORE) investigators. J Am Med Assoc 282:637–645CrossRef

16.

Harris S, Watts N, Genant H, McKeever C, Hangartner T, Keller M et al. (1999) Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. Vertebral efficacy with risedronate therapy (VERT) study group. J Am Med Assoc 282:1344–1352CrossRef

17.

Neer R, Arnaud C, Zanchetta J, Prince R, Gaich G, Reginster J et al. (2001) Effect of parathyroid hormone (1–34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med 344:1434–1441PubMed

18.

Torgerson D, Bell-Syer S (2001) Hormone replacement therapy and prevention of nonvertebral fractures: a meta-analysis of randomized trials. J Am Med Assoc 285:2891–2897CrossRef

19.

Lufkin E, Wahner H, O’Fallon W, Hodgson S, Kotowicz M, Lane A et al. (1992) Treatment of postmenopausal osteoporosis with transdermal estrogen. Ann Intern Med 117:1–9PubMed

20.

Cranney A, Guyatt G, Krolicki N, Welch V, Griffith L, Adachi J et al. (2001) A meta-analysis of etidronate for the treatment of postmenopausal osteoporosis. Osteoporos Int 12:140–151CrossRefPubMed

21.

Chesnut C, Silverman S, Andriano K, Genant H, Gimona A, Harris S et al. (2000) A randomized trial of nasal spray salmon calcitonin in postmenopausal women with established osteoporosis: the prevent recurrence of osteoporotic fractures study. Am J Med 109:267–276CrossRefPubMed

22.

Haussler MR (1986) Vitamin D receptors: nature and function. Annu Rev Nutr 6:527–562CrossRefPubMed

23.

Pike JW (1991) Vitamin D receptors: structure and function in transcription. Annu Rev Nutr 11:189–216CrossRefPubMed

24.

Lian JB, Stein GS, Owen TA et al. (1991) Vitamin D regulation of the bone-specific osteocalcin gene is functionally related to osteoblast growth and differentiation. In: Norman AW, Bouillon R, Thomasset M (eds) Vitamin D: gene regulation, structure-function analysis and clinical application. De Gruyter, Berlin, pp 12–20

25.

Abe E, Miyaura C, Sakagami H et al. (1981) Differentiation of mouse myeloid leukemia cells induced by 1α, 25-dihydroxyvitamin D3. Proc Natl Acad Sci USA 78:4990–4994PubMed

26.

McSheehy PM, Chambers TJ (1987) 1.25-dihydroxyvitamin D3 stimulates rat osteoblastic cells to release a soluble factor that increases osteoclastic bone resorption. J Clin Invest 80:425–429PubMed

27.

Dechant KL, Goa KL (1994) Calcitriol: a review of its use in the treatment of postmenopausal osteoporosis and its potential in corticosteroid-induced osteoporosis. Drugs Aging 5:300–317PubMed

28.

Jones G, Hogan DB, Yendt E, Hanley DA (1996) Vitamin D metabolites and analogs in the treatment of osteoporosis. Can Med Assoc J 155:955–961

29.

Tsai KS, Heath H III, Kumar R et al. (1984) Impaired vitamin D metabolism with aging in women. J Clin Invest 73:1668–1672

30.

Watson PH, Hanley DA (1993) Parathyroid hormone: regulation of synthesis and secretion. Clin Invest Med 16:58–77PubMed

31.

Baron R (1993) Anatomy and ultrastructure of bone. In: Favus MJ (ed) Primer on the metabolic bone diseases and disorders of mineral metabolism, 2nd edn. Raven Press, New York, pp 3–9

32.

Riggs BL, Nelson KL (1985) Effect of long-term treatment with calcitriol on calcium absorption and mineral metabolism in postmepenopausal osteoporosis. J Clin Endocrinol Metab 61:457–461PubMed

33.

Lund BJ, Sorensen OH, Lund BI et al. (1982) Serum 1.25-dihydroxyvitamin D in normal subjects and in patients with postmenopausal osteopenia: influence of age, renal function and oestrogen therapy. Horm Metab Res 14:271–274PubMed

34.

Gallagher JC, Riggs BL, Eisman J et al. (1979) Intestinal calcium absorption and serum vitamin D metabolites in normal subjects and osteoporotic patients. J Clin Invest 64:729–736PubMed

35.

Nguyen T, Sambrook P, Kelly P (1993) Prediction of osteoporotic fractures by postmenopausal instability in bone density. Br Med J 307:1111–1115

36.

Eisman JA (1995) Efficacy of treatment of osteoporotic fracture. Am J Med 98 (Suppl 2a):17–23CrossRef

37.

Dickersin K, Scherer R, Lefebvre C (1994) Identifying the relevant studies for systematic reviews. Br Med J 309:1286–1291

38.

Jadad AR, Moore RA, Carroll D, Jenkinson C (1996) Assessing the quality of reports of randomized clinical trials: Is blinding necessary? Control Clin Trials 17:1–12PubMed

39.

Egger M, Smith GD, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. Br Med J 315:629–634

40.

Aloia JF, Vaswani A, Yeh JK, Ellis K, Yasumura S, Cohn S (1988) Calcitriol in the treatment of postmenopausal osteoporosis. Am J Med 84:401–408PubMed

41.

Ebeling PR, Wark JD, Yeung S, Poon C, Salehi N, Nicholson GC et al. (2001) Effects of calcitriol or calcium on bone mineral density, bone turnover, and fractures in men with primary osteoporosis: a two-year randomized, double-blind, double-placebo study. J Clin Endocr Metab 86:4096–4103

42.

Gallagher JC, Riggs BL, Recker RR, Goldgar D (1989) The effect of calcitriol on patients with postmenopausal osteoporosis with special reference to fracture frequency. Soc Exper Biol Med 287–292

43.

Gallagher JC, Goldgar D (1990) Treatment of postmenopausal osteoporosis with high doses of synthetic calcitriol. Ann Intern Med 113:649–655PubMed

44.

Gallagher JC, Fowler SE, Detter JR, Sherman SS (2001) Combination treatment with estrogen and calcitriol in the prevention of age-related bone loss. J Clin Endocrinol Metab 86:3618–3628

45.

Hayashi Y, Fujita T, Inoue T (1992) Decrease of vertebral fracture in osteoporosis by administration of 1α-hydroxy-vitamin D3. JBMM 10:184–188

46.

Lakatos P, Nagy Z, Kiss L, Horvath C, Takacs I, Foldes J et al. (2000) Prevention of corticosteroid-induced osteoporosis by alphacalcidol. Z Rheumatol 59 (Suppl 1):48–52CrossRefPubMed

47.

Lambrinoudaki I, Chan DT, Lau CS, Wong RW, Yeung SS, Kung AW (2000) Effect of calcitriol on bone mineral density in premenopausal Chinese women taking chronic steroid therapy: a randomized, double-blind, placebo-controlled study. J Rheumatol 27:1759–1765PubMed

48.

Menczel J, Foldes J, Steinberg R, Leichter I, Shalita B, Bdolah-Abram T et al. (1994) Alfacalcidol (Alpha D3) and calcium in osteoporosis. Clin Orthop 300:241–247PubMed

49.

Orimo H, Shiraki M, Hayashi Y, Hoshino T, Onaya T, Miyazaki S et al. (1994) Effects of 1α-hydroxyvitamin D3 on lumbar bone mineral density and vertebral fractures in patients with postmenopausal osteoporosis. Calcif Tissue Int 54:370–376PubMed

50.

Reginster JY, Kuntz D, Verdicht W, Wouters M, Guillevin L, Menkes CJ et al. (1999) Prophylactic use of alfacalcidol in corticosteroid-induced osteoporosis. Bone 9:75–81CrossRef

51.

Sambrook P, Birmingham J, Kelly P, Kempler S, Nguyen T, Pocock N et al. (1993) Prevention of corticosteroid osteoporosis: a comparison of calcium, calcitriol, and calcitonin. N Engl J Med 328:1747–1752CrossRefPubMed

52.

Sambrook P, Henderson NK, Keogh A, Macdonald P, Glanville A, Spratt P (2000) Effect of calcitriol on bone loss after cardiac or lung transplantation. J Bone Miner Res 15:1818–1824PubMed

53.

Sato Y, Manabe S, Kuno H, Oizumi K (1999) Amelioration of osteopenia and hypovitaminosis D by 1α-hydroxyvitamin D3 in elderly patients with Parkinson’s disease. J Neurosurg Psychiatry 66:64–68

54.

Sato Y, Maruoka H, Oizumi K (1997) Amelioration of hemiplegia-associated osteopenia more than 4 years after stroke by 1α-hydroxyvitamin D3 and calcium supplementation. Stroke 28:736–739PubMed

55.

Shiraki M, Kushida K, Yamazaki K, Nagai T, Inoue T, Orimo H (1996) Effects of 2 years’ treatment of osteoporosis with 1α-hydroxy vitamin D3 on bone mineral density and incidence of fracture: a placebo-controlled, double-blind prospective study. Endocrinol J 43:211–220

56.

Tilyard MW, Spears GFS, Thomson J, Dovey S (1992) Treatment of postmenopausal osteoporosis with calcitriol and calcium. N Engl J Med 326:357–362

57.

Altman DG, Schulz KF, Moher D, Egger M, Davidoff F, Elbourne D (2001) The revised CONSORT statement for reporting randomized trials: explanation and elaboration. Ann Intern Med 134:663–694PubMed

58.

Stempfle HU, Werner C, Echtler S, Wehr U, Rambeck WA, Siebert U et al. (1999) Prevention of osteoporosis after cardiac transplantation. Transplantation 68:523–530PubMed

59.

Ott SM, Chesnut CH (1989) Calcitriol treatment is not effective in postmenopausal osteoporosis. Ann Intern Med 110:267–274PubMed

60.

Cranney A, Guyatt G, Griffith L, Wells G, Tugwell P, Rosen C et al. (2002) Summary of meta-analyses of therapies for postmenopausal osteoporosis. Endocrinol Rev 23:570–578CrossRef

61.

Homik J, Cranney A, Shea B, Tugwell P, Wells G, Adachi R et al. (2003) Biphosphonates for steroid induced osteoporosis (Cochrane review). The Cochrane Library, issue 4, Chichester, UK

62.

Cranney A, Welch V, Adachi JD, Homik J, Shea B, Suarez-Almazor ME et al. (2003) Calcitonin for preventing and treating corticosteroid-induced osteoporosis (Cochrane review). The Cochrane Library, issue 4, Chichester, UK

63.

ACR task force on osteoporosis guidelines (1996) Recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis. Arthritis Rheum 39:1791–1801PubMed

64.

Ringe JD, Cöster A, Meng T, Schacht E, Umbach R (1999) Treatment of glucocorticoid-induced osteoporosis with alphacalcidol versus vitamin D/calcium. Calcif Tissue Int 65:337–340CrossRefPubMed

65.

Sterne JA, Gavaghan D, Egger M (2000) Publication and related bias in meta-analysis: power of statistical tests and prevalence in the literature. J Clin Epidemiol 53:1119–1129CrossRefPubMed

Title: Efficacy of alphacalcidol and calcitriol in primary and corticosteroid-induced osteoporosis: a meta-analysis of their effects on bone mineral density and fracture rate
Authors: Florent Richy
Olivier Ethgen
Olivier Bruyere
Jean-Yves Reginster
Publication date: 01-04-2004
Publisher: Springer-Verlag
Published in: Osteoporosis International / Issue 4/2004
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI: https://doi.org/10.1007/s00198-003-1570-5

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Efficacy of alphacalcidol and calcitriol in primary and corticosteroid-induced osteoporosis: a meta-analysis of their effects on bone mineral density and fracture rate

Abstract

Keynote webinar | Spotlight on sleep in brain health

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Abstract

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