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Vitamin D Status and Parathyroid Hormone Concentrations Influence the Skeletal Response to Zoledronate and Denosumab

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Abstract

Studies suggest that optimal vitamin D status is required for the maximal effect of antiresorptive agents. We investigated the relationship between vitamin D status, serum parathyroid hormone (PTH) concentrations, and change in bone mineral density (BMD) following iv zoledronate and denosumab. We carried out a retrospective analysis of 111 patients, mean age 70 (SD 13) years, 89 women and 22 men, prescribed zoledronate and 43 postmenopausal women treated with denosumab for osteoporosis. We measured BMD at the lumbar spine (LS) and total hip (TH), serum 25 (OH) vitamin D, PTH, and bone turnover markers (plasma CTX, P1NP) at 1 year. In patients on zoledronate, BMD increased at the LS and TH (mean LS change [SEM] = 2.6 % [0.5 %], mean TH change = 1.05 % [0.5 %], p < 0.05). A significant increase in BMD was seen at the LS only in the denosumab group (p = 0.001). Significant decreases in CTX and P1NP were observed at 12 months in both treatment groups. At baseline and at 12 months, 34 % and 23 % of the patients on zoledronate had a serum vitamin D of <50 nmol/L, respectively. The mean PTH concentration in patients with 25 (OH) vitamin D <50 nmol/L was 44 ng/L (SEM 16.6). Patients with PTH concentration <44 ng/L had significantly higher increases in TH BMD compared to those with PTH >44 ng/L (zoledronate 1.9 [0.83] vs. −0.43 [0.81], p = 0.04; denosumab 4.1 [0.054] vs. −1.7 [0.04], p = 0.004). Optimal vitamin D status and PTH concentrations improve the skeletal response to zoledronate and denosumab.

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References

  1. Bischoff-Ferrari HA, Willett WC, Wong JB, Giovannucci E, Dietrich T, Dawson-Hughes B (2005) Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials. JAMA 293(18):2257–2264

    Article  PubMed  CAS  Google Scholar 

  2. Lips P, Duong T, Oleksik A, Black D, Cummings S, Cox D et al (2001) A global study of vitamin D status and parathyroid function in postmenopausal women with osteoporosis: baseline data from the multiple outcomes of raloxifene evaluation clinical trial. J Clin Endocrinol Metab 86(3):1212–1221

    Article  PubMed  CAS  Google Scholar 

  3. 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(9041):1535–1541

    Article  PubMed  CAS  Google Scholar 

  4. Black DM, Delmas PD, Eastell R, Reid IR, Boonen S, Cauley JA et al (2007) Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med 356(18):1809–1822

    Article  PubMed  CAS  Google Scholar 

  5. Cummings SR, San Martin J, McClung MR, Siris ES, Eastell R, Reid IR et al (2009) Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med 361(8):756–765

    Article  PubMed  CAS  Google Scholar 

  6. Adami S, Giannini S, Bianchi G, Sinigaglia L, Di Munno O, Fiore CE et al (2009) Vitamin D status and response to treatment in post-menopausal osteoporosis. Osteoporos Int 20(2):239–244

    Article  PubMed  CAS  Google Scholar 

  7. Carmel AS, Shieh A, Bang H, Bockman RS (2012) The 25 (OH) D level needed to maintain a favorable bisphosphonate response is ≥33 ng/mL. Osteoporos Int 23(10):2479–2487

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  8. Adami S, Isaia G, Luisetto G, Minisola S, Sinigaglia L, Gentilella R et al (2006) Fracture incidence and characterization in patients on osteoporosis treatment: the ICARO study. J Bone Miner Res 21(10):1565–1570

    Article  PubMed  CAS  Google Scholar 

  9. Ishijima M, Sakamoto Y, Yamanaka M, Tokita A, Kitahara K, Kaneko H et al (2009) 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

    Article  PubMed  CAS  Google Scholar 

  10. Barone A, Giusti A, Pioli G, Girasole G, Razzano M, Pizzonia M et al (2007) 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

    Article  PubMed  Google Scholar 

  11. Bonnick S, Broy S, Kaiser F, Teutsch C, Rosenberg E, DeLucca P et al (2007) Treatment with alendronate plus calcium, alendronate alone, or calcium alone for postmenopausal low bone mineral density. Curr Med Res Opin 23(6):1341–1349

    Article  PubMed  CAS  Google Scholar 

  12. Antoniucci DM, Vittinghoff E, Palermo L, Black DM, Sellmeyer DE (2009) Vitamin D insufficiency does not affect response of bone mineral density to alendronate. Osteoporos Int 20(7):1259–1266

    Article  PubMed  CAS  Google Scholar 

  13. Li L, Roddam A, Gitlin M, Taylor A, Shepherd S, Shearer A et al (2012) Persistence with osteoporosis medications among postmenopausal women in the UK General Practice Research Database. Menopause 19(1):33–40

    Article  PubMed  CAS  Google Scholar 

  14. Bourke S, Bolland MJ, Grey A, Horne AM, Wattie DJ, Wong S et al (2013) The impact of dietary calcium intake and vitamin D status on the effects of zoledronate. Osteoporos Int 24(1):349–354

    Article  PubMed  CAS  Google Scholar 

  15. Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK et al (2011) The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab 96(1):53–58

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  16. Aspray TJ, Francis RM (2012) Treatment of osteoporosis in women intolerant of oral bisphosphonates. Maturitas 71(1):76–78

    Article  PubMed  CAS  Google Scholar 

  17. Hadji P, Claus V, Ziller V, Intorcia M, Kostev K, Steinle T (2012) GRAND: the German retrospective cohort analysis on compliance and persistence and the associated risk of fractures in osteoporotic women treated with oral bisphosphonates. Osteoporos Int 23(1):223–231

    Article  PubMed  CAS  Google Scholar 

  18. Rossini M, Bianchi G, Di Munno O, Giannini S, Minisola S, Sinigaglia L et al (2006) Determinants of adherence to osteoporosis treatment in clinical practice. Osteoporos Int 17(6):914–921

    Article  PubMed  CAS  Google Scholar 

  19. Rossini M, Gatti D, Viapiana O, Fracassi E, Idolazzi L, Zanoni S et al (2012) Short-term effects on bone turnover markers of a single high dose of oral vitamin D3. J Clin Endocrinol Metab 97(4):E622–E626

    Article  PubMed  CAS  Google Scholar 

  20. Atkins GJ, Anderson PH, Findlay DM, Welldon KJ, Vincent C, Zannettino AC et al (2007) Metabolism of vitamin D3 in human osteoblasts: evidence for autocrine and paracrine activities of 1alpha, 25-dihydroxyvitamin D3. Bone 40(6):1517–1528

    Article  PubMed  CAS  Google Scholar 

  21. van Driel M, Koedam M, Buurman CJ, Hewison M, Chiba H, Uitterlinden AG et al (2006) Evidence for auto/paracrine actions of vitamin D in bone: 1alpha-hydroxylase expression and activity in human bone cells. FASEB J 20(13):2417–2419

    Article  PubMed  CAS  Google Scholar 

  22. Kogawa M, Findlay DM, Anderson PH, Ormsby R, Vincent C, Morris HA et al (2010) Osteoclastic metabolism of 25 (OH)-vitamin D3: a potential mechanism for optimization of bone resorption. Endocrinology 151(10):4613–4625

    Article  PubMed  CAS  Google Scholar 

  23. Civitelli R, Ziambaras K (2011) Calcium and phosphate homeostasis: concerted interplay of new regulators. J Endocrinol Invest 34(7 Suppl):3–7

    PubMed  CAS  Google Scholar 

  24. Lips P (2001) Vitamin D deficiency and secondary hyperparathyroidism in the elderly: consequences for bone loss and fractures and therapeutic implications. Endocr Rev 22(4):477–501

    Article  PubMed  CAS  Google Scholar 

  25. Deane A, Constancio L, Fogelman I, Hampson G (2007) 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

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  26. Anastasilakis AD, Toulis KA, Polyzos SA, Anastasilakis CD, Makras P (2012) Long-term treatment of osteoporosis: safety and efficacy appraisal of denosumab. Ther Clin Risk Manag 8:295–306

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  27. Makras P, Polyzos SA, Papatheodorou A, Kokkoris P, Chatzifotiadis D, Anastasilakis AD (2013) Parathyroid hormone changes following denosumab treatment in postmenopausal osteoporosis. Clin Endocrinol (Oxf) 79:499–503

    Article  CAS  Google Scholar 

  28. Bekker PJ, Holloway DL, Rasmussen AS, Murphy R, Martin SW, Leese PT et al (2004) A single-dose placebo-controlled study of AMG 162, a fully human monoclonal antibody to RANKL, in postmenopausal women. J Bone Miner Res 19(7):1059–1066

    Article  PubMed  CAS  Google Scholar 

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Acknowledgment

I. F. has received previous research support from Novartis and anticipates receiving a Grant from Amgen.

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Authors and Affiliations

  1. Department of Clinical Chemistry, St Thomas’ Hospital, 5th Floor, North Wing, Lambeth Palace Road, London, SE1 7EH, UK

    P. Mosali, L. Bernard, M. Ewang & G. Hampson

  2. Metabolic Bone Clinic, Department of Rheumatology, Guy’s Hospital, London, SE1 9RT, UK

    P. Mosali, L. Bernard, J. Wajed, M. Ewang, I. Fogelman & G. Hampson

  3. Osteoporosis Unit, Guy’s Hospital, London, SE1 9RT, UK

    Z. Mohamed, A. Moore & I. Fogelman

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  1. P. Mosali
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  2. L. Bernard
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  3. J. Wajed
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  4. Z. Mohamed
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  5. M. Ewang
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  6. A. Moore
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  7. I. Fogelman
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  8. G. Hampson
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Correspondence to G. Hampson.

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All authors have no conflict of interest to declare.

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Mosali, P., Bernard, L., Wajed, J. et al. Vitamin D Status and Parathyroid Hormone Concentrations Influence the Skeletal Response to Zoledronate and Denosumab. Calcif Tissue Int 94, 553–559 (2014). https://doi.org/10.1007/s00223-014-9840-0

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  • DOI: https://doi.org/10.1007/s00223-014-9840-0

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