Use of vitamin D with anti-osteoporotic drugs: are available clinical trials telling us the whole story?
Endocrine . 2023 Oct 10. doi: 10.1007/s12020-023-03551-z
Luigi di Filippo 1, Fabio Massimo Ulivieri 2, Ranuccio Nuti 3, Andrea Giustina 1
There is a strong rationale for using vitamin D in combination with anti-osteoporotic drugs. Still, available trials do not give clear indications in this setting, presenting a suboptimal and heavily inhomogeneous experimental design. Health authorities should revise requirements for using vitamin D in anti-osteoporotic drug trials to maximise their effect and produce reliable indications for clinical practice in this setting.
51 references
- G. Mazziotti, J. Bilezikian, E. Canalis, D. Cocchi, A. Giustina, New understanding and treatments for osteoporosis. Endocrine 41(1), 58–69 (2012). https://doi.org/10.1007/s12020-011-9570-2 - DOI - PubMed
- J.P. Bilezikian, A.M. Formenti, R.A. Adler et al. Vitamin D: dosing, levels, form, and route of administration: does one approach fit all? Rev Endocr Metab Disord 22(4), 1201–1218 (2021). https://doi.org/10.1007/s11154-021-09693-7 - DOI - PubMed - PMC
- A.G. Need, P.D. O’Loughlin, H.A. Morris, P.S. Coates, M. Horowitz, B.E. Nordin, Vitamin D metabolites and calcium absorption in severe vitamin D deficiency. J Bone Miner Res 23(11), 1859–1863 (2008). https://doi.org/10.1359/jbmr.080607 - DOI - PubMed
- M. Kužma, P. Jackuliak, Z. Killinger, J. Payer, Parathyroid hormone-related changes of bone structure. Physiol Res 70(Suppl 1), S3–S11 (2021). https://doi.org/10.33549/physiolres.934779 - DOI - PubMed - PMC
- L. di Filippo, A. Allora, M. Locatelli et al. Hypocalcemia in COVID-19 is associated with low vitamin D levels and impaired compensatory PTH response. Endocrine 74(2), 219–225 (2021). https://doi.org/10.1007/s12020-021-02882-z - DOI - PubMed - PMC
- A. Giustina, R. Bouillon, N. Binkley et al. Controversies in Vitamin D: a statement from the third international conference. JBMR Plus 4(12), e10417 (2020). https://doi.org/10.1002/jbm4.10417 - DOI - PubMed - PMC
- S.H. Ralston, N. Binkley, S. Boonen et al. Randomized trial of alendronate plus vitamin D3 versus standard care in osteoporotic postmenopausal women with vitamin D insufficiency. Calcif Tissue Int 88(6), 485–494 (2011). https://doi.org/10.1007/s00223-011-9482-4 - DOI - PubMed
- A. Catalano, F. Bellone, D. Santoro et al. Vitamin D boosts alendronate tail effect on bone mineral density in postmenopausal women with osteoporosis. Nutrients 13(6), 1878 (2021). https://doi.org/10.3390/nu13061878 - DOI - PubMed - PMC
- C. Roux, N. Binkley, S. Boonen, et al. Vitamin D status and bone mineral density changes during alendronate treatment in postmenopausal osteoporosis [published correction appears in Calcif Tissue Int. 2014 Feb;94(2):158. Regnister, Jean-Yves corrected to Reginster, Jean-Yves]. Calcif Tissue Int 94(2), 153–157 (2014). https://doi.org/10.1007/s00223-013-9763-1
- S. Adami, G. Isaia, G. Luisetto et al. Fracture incidence and characterization in patients on osteoporosis treatment: the ICARO study. J Bone Miner Res 21(10), 1565–1570 (2006). https://doi.org/10.1359/jbmr.060715 - DOI - PubMed
- S. Adami, S. Giannini, G. Bianchi et al. Vitamin D status and response to treatment in post-menopausal osteoporosis. Osteoporos Int 20(2), 239–244 (2009). https://doi.org/10.1007/s00198-008-0650-y - DOI - PubMed
- A. Deane, L. Constancio, I. Fogelman, G. Hampson, The impact of vitamin D status on changes in bone mineral density during treatment with bisphosphonates and after discontinuation following long-term use in post-menopausal osteoporosis. BMC Musculoskelet Disord 8, 3 (2007). https://doi.org/10.1186/1471-2474-8-3 - DOI - PubMed - PMC
- M. Ishijima, Y. Sakamoto, M. Yamanaka et al. Minimum required vitamin D level for optimal increase in bone mineral density with alendronate treatment in osteoporotic women. Calcif Tissue Int 85(5), 398–404 (2009). https://doi.org/10.1007/s00223-009-9295-x - DOI - PubMed
- A. Catalano, N. Morabito, A. Di Stefano et al. Vitamin D and bone mineral density changes in postmenopausal women treated with strontium ranelate. J Endocrinol Invest 38(8), 859–863 (2015). https://doi.org/10.1007/s40618-015-0299-2 - DOI - PubMed
- A. Barone, A. Giusti, G. Pioli et al. Secondary hyperparathyroidism due to hypovitaminosis D affects bone mineral density response to alendronate in elderly women with osteoporosis: a randomized controlled trial. J Am Geriatr Soc 55(5), 752–757 (2007). https://doi.org/10.1111/j.1532-5415.2007.01161.x - DOI - PubMed
- J.L. Geller, B. Hu, S. Reed, J. Mirocha, J.S. Adams, Increase in bone mass after correction of vitamin D insufficiency in bisphosphonate-treated patients. Endocr Pract 14(3), 293–297 (2008). https://doi.org/10.4158/EP.14.3.293 - DOI - PubMed
- G.A. Heckman, A. Papaioannou, R.J. Sebaldt et al. Effect of vitamin D on bone mineral density of elderly patients with osteoporosis responding poorly to bisphosphonates. BMC Musculoskelet Disord 3, 6 (2002). https://doi.org/10.1186/1471-2474-3-6 - DOI - PubMed - PMC
- R. Okazaki, R. Muraoka, M. Maehara, D. Inoue, Factors associated with inadequate responses to risedronate in Japanese patients with osteoporosis. J Bone Miner Metab 37(1), 185–197 (2019). https://doi.org/10.1007/s00774-018-0931-2 - DOI - PubMed
- O.C. Kwon, J.S. Oh, M.C. Park, Y.G. Kim, Effect of Vitamin D supplementation on bone mineral density in rheumatoid arthritis patients with osteoporosis. Front Med 7, 443 (2020). https://doi.org/10.3389/fmed.2020.00443 - DOI
- U.A. Liberman, S.R. Weiss, J. Bröll et al. Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal osteoporosis. The Alendronate Phase III Osteoporosis Treatment Study Group. N Engl J Med 333(22), 1437–1443 (1995). https://doi.org/10.1056/NEJM199511303332201 - DOI - PubMed
- D.M. Black, S.R. Cummings, D.B. Karpf et al. Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Fracture Intervention Trial Research Group. Lancet 348(9041), 1535–1541 (1996). https://doi.org/10.1016/s0140-6736(96)07088-2 - DOI - PubMed
- S.R. Cummings, D.M. Black, D.E. Thompson et al. Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the Fracture Intervention Trial. JAMA 280(24), 2077–2082 (1998). https://doi.org/10.1001/jama.280.24.2077 - DOI - PubMed
- K.G. Saag, R. Emkey, T.J. Schnitzer et al. Alendronate for the prevention and treatment of glucocorticoid-induced osteoporosis. Glucocorticoid-Induced Osteoporosis Intervention Study Group. N Engl J Med 339(5), 292–299 (1998). https://doi.org/10.1056/NEJM199807303390502 - DOI - PubMed
- B. Ettinger, D.M. Black, B.H. Mitlak et al. 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 published correction appears in JAMA 1999 Dec 8;282(22):2124. JAMA. 282(7), 637–645 (1999). https://doi.org/10.1001/jama.282.7.637 - DOI - PubMed
- S.T. Harris, N.B. Watts, H.K. Genant et al. 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. JAMA 282(14), 1344–1352 (1999). https://doi.org/10.1001/jama.282.14.1344 - DOI - PubMed
- E. Orwoll, M. Ettinger, S. Weiss et al. Alendronate for the treatment of osteoporosis in men. N Engl J Med 343(9), 604–610 (2000). https://doi.org/10.1056/NEJM200008313430902 - DOI - PubMed
- S. Wallach, S. Cohen, D.M. Reid et al. Effects of risedronate treatment on bone density and vertebral fracture in patients on corticosteroid therapy. Calcif Tissue Int 67(4), 277–285 (2000). https://doi.org/10.1007/s002230001146 - DOI - PubMed
- J. Reginster, H.W. Minne, O.H. Sorensen et al. Randomized trial of the effects of risedronate on vertebral fractures in women with established postmenopausal osteoporosis. Vertebral Efficacy with Risedronate Therapy (VERT) Study Group. Osteoporos Int 11(1), 83–91 (2000). https://doi.org/10.1007/s001980050010 - DOI - PubMed
- M.R. McClung, P. Geusens, P.D. Miller et al. Effect of risedronate on the risk of hip fracture in elderly women. Hip Intervention Program Study Group. N Engl J Med 344(5), 333–340 (2001). https://doi.org/10.1056/NEJM200102013440503 - DOI - PubMed
- J.D. Adachi, K.G. Saag, P.D. Delmas, et al., Two-year effects of alendronate on bone mineral density and vertebral fracture in patients receiving glucocorticoids: a randomized, double-blind, placebo-controlled extension trial. Arthritis Rheum 44(1), 202–211 (2001). https://doi.org/10.1002/1529-0131(200101)44:1<202::AID-ANR27>3.0.CO;2-W - DOI - PubMed
- R.M. Neer, C.D. Arnaud, J.R. Zanchetta et al. Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med 344(19), 1434–1441 (2001). https://doi.org/10.1056/NEJM200105103441904 - DOI - PubMed
- E. Barrett-Connor, D. Grady, A. Sashegyi et al. Raloxifene and cardiovascular events in osteoporotic postmenopausal women: four-year results from the MORE (Multiple Outcomes of Raloxifene Evaluation) randomized trial. JAMA 287(7), 847–857 (2002). https://doi.org/10.1001/jama.287.7.847 - DOI - PubMed
- C.H. Chesnut 3rd, A. Skag, C. Christiansen et al. Effects of oral ibandronate administered daily or intermittently on fracture risk in postmenopausal osteoporosis. J Bone Miner Res 19(8), 1241–1249 (2004). https://doi.org/10.1359/JBMR.040325 - DOI - PubMed
- P.J. Meunier, C. Roux, E. Seeman et al. The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis. N Engl J Med 350(5), 459–468 (2004). https://doi.org/10.1056/NEJMoa022436 - DOI - PubMed
- E. McCloskey, P. Selby, M. Davies et al. Clodronate reduces vertebral fracture risk in women with postmenopausal or secondary osteoporosis: results of a double-blind, placebo-controlled 3-year study. J Bone Miner Res 19(5), 728–736 (2004). https://doi.org/10.1359/JBMR.040116 - DOI - PubMed
- J.Y. Reginster, E. Seeman, M.C. De Vernejoul, et al. Strontium ranelate reduces the risk of nonvertebral fractures in postmenopausal women with osteoporosis: Treatment of Peripheral Osteoporosis (TROPOS) study. J Clin Endocrinol Metab 90(5), 2816–2822 (2005). https://doi.org/10.1210/jc.2004-1774 - DOI - PubMed
- D.M. Black, P.D. Delmas, R. Eastell et al. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med 356(18), 1809–1822 (2007). https://doi.org/10.1056/NEJMoa067312 - DOI - PubMed
- K.G. Saag, E. Shane, S. Boonen et al. Teriparatide or alendronate in glucocorticoid-induced osteoporosis. N Engl J Med 357(20), 2028–2039 (2007). https://doi.org/10.1056/NEJMoa071408 - DOI - PubMed
- K.W. Lyles, C.S. Colón-Emeric, J.S. Magaziner et al. Zoledronic acid and clinical fractures and mortality after hip fracture. N Engl J Med 357(18), 1799–1809 (2007). https://doi.org/10.1056/NEJMoa074941 - DOI - PubMed
- E.V. McCloskey, M. Beneton, D. Charlesworth et al. Clodronate reduces the incidence of fractures in community-dwelling elderly women unselected for osteoporosis: results of a double-blind, placebo-controlled randomized study. J Bone Miner Res 22(1), 135–141 (2007). https://doi.org/10.1359/jbmr.061008 - DOI - PubMed
- S.L. Silverman, C. Christiansen, H.K. Genant et al. Efficacy of bazedoxifene in reducing new vertebral fracture risk in postmenopausal women with osteoporosis: results from a 3-year, randomized, placebo-, and active-controlled clinical trial. J Bone Miner Res 23(12), 1923–1934 (2008). https://doi.org/10.1359/jbmr.080710 - DOI - PubMed
- S.R. Cummings, J. San Martin, M.R. McClung et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis published correction appears in N Engl J Med. 2009 Nov 5;361(19):1914. N Engl J Med. 361(8), 756–765 (2009). https://doi.org/10.1056/NEJMoa0809493 - DOI - PubMed
- F. Cosman, D.B. Crittenden, J.D. Adachi et al. Romosozumab treatment in postmenopausal women with osteoporosis. N Engl J Med 375(16), 1532–1543 (2016). https://doi.org/10.1056/NEJMoa1607948 - DOI - PubMed
- K.G. Saag, J. Petersen, M.L. Brandi et al. Romosozumab or Alendronate for Fracture Prevention in Women with Osteoporosis. N Engl J Med 377(15), 1417–1427 (2017). https://doi.org/10.1056/NEJMoa1708322 - DOI - PubMed
- P.R. Ebeling, R.A. Adler, G. Jones et al. Management of endocrine disease: therapeutics of vitamin D. Eur J Endocrinol 179(5), R239–R259 (2018). https://doi.org/10.1530/EJE-18-0151 - DOI - PubMed
- M. Rossini, S. Adami, F. Bertoldo et al. Linee guida per la diagnosi, la prevenzione ed il trattamento dell’osteoporosi. Reumatismo 68(1), 1–42 (2016) - DOI - PubMed
- M.F. Holick, The vitamin D deficiency pandemic: approaches for diagnosis, treatment and prevention. Rev Endocr Metab Disord 18(2), 153–165 (2017). https://doi.org/10.1007/s11154-017-9424-1 - DOI - PubMed
- European Medicines Agency: evaluation of new medicinal products in the treatment of primary osteoporosis - Scientific guideline. London, November 2006. Doc. Ref. CPMP/EWP/552/95 Rev. 2. www.ema.europa.eu/en/evaluation-new-medicinal-products-treatment-primary...
- M. Hiligsmann, W. Ben Sedrine, O. Bruyère, S.M. Evers, V. Rabenda, J.Y. Reginster, Cost-effectiveness of vitamin D and calcium supplementation in the treatment of elderly women and men with osteoporosis. Eur J Public Health 25(1), 20–25 (2015). https://doi.org/10.1093/eurpub/cku119 - DOI - PubMed
- S. Minisola, L. Colangelo, C. Cipriani, J. Pepe, D.P. Cook, C. Mathieu, Screening for hypovitaminosis D: cost-effective or not? Eur J Endocrinol 180(3), D1–D7 (2019). https://doi.org/10.1530/EJE-18-0977 - DOI - PubMed
- C.T. Sempos, A.C. Heijboer, D.D. Bikle, J. Bollerslev, R. Bouillon, P.M. Brannon, H.F. DeLuca, G. Jones, C.F. Munns, J.P. Bilezikian, A. Giustina, N. Binkley, Vitamin D assays and the definition of hypovitaminosis D: results from the First International Conference on Controversies in Vitamin D. Br J Clin Pharmacol 84(10), 2194–2207 (2018) - DOI - PubMed - PMC
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