Activated vitamin D3 formulations can be safely used as concomitant medication for prevention of denosumab-induced hypocalcemia in women with postmenopausal osteoporosis

J Obstet Gynaecol Res. 2019 Apr;45(4):908-914. doi: 10.1111/jog.13913. Epub 2019 Jan 7.

Abstract

Aim: Denosumab prevents osteoporosis by potently inhibiting bone resorption, but requires oral therapy with calcium and vitamin D preparations to prevent the side effects of hypocalcemia. Generally, a combination drug containing calcium, natural vitamin D, and magnesium is used. However, if activated vitamin D has been used before the initiation of denosumab therapy, continued use of activated vitamin D is not uncommon. This study aimed to evaluate the combination vitamin D preparation, alfacalcidol, and eldecalcitol on the therapeutic effect on denosumab therapy, the preventive effect on hypocalcemia, and the effect on renal function, to determine the optimal choice of concomitant medication.

Methods: This is a retrospective and single-center study. Among 39 patients who had used denosumab (60 mg dose) for at least 12 months between November 2013 and October 2015, those who used the combination medication concomitantly as the standard treatment, those who used alfacalcidol concomitantly, and those who used eldecalcitol concomitantly were compared.

Results: Denosumab therapy markedly increased lumbar spine and femoral neck bone densities at 12 months in the three groups, showing no particular difference in the rate of increase of bone density. The three groups had marked decreases in bone metabolism markers, but had no intergroup differences. No hypocalcemia, hypercalcemia, or obvious renal dysfunction occurred over 12 months.

Conclusion: This study indicates that the use of activated vitamin D preparations, as concomitant medications with denosumab therapy, is appropriate considering the therapeutic efficacy of denosumab, prevention of hypocalcemia, and influence on renal function.

Keywords: calcium; denosumab; hypocalcemia; osteoporosis; vitamin D.

MeSH terms

  • Aged
  • Bone Density Conservation Agents / adverse effects*
  • Denosumab / administration & dosage
  • Denosumab / adverse effects
  • Denosumab / pharmacology*
  • Drug Therapy, Combination
  • Female
  • Humans
  • Hydroxycholecalciferols / administration & dosage
  • Hydroxycholecalciferols / pharmacology*
  • Hypocalcemia / chemically induced
  • Hypocalcemia / drug therapy*
  • Middle Aged
  • Osteoporosis, Postmenopausal / drug therapy*
  • Outcome Assessment, Health Care*
  • Retrospective Studies
  • Vitamin D / administration & dosage
  • Vitamin D / analogs & derivatives
  • Vitamin D / pharmacology

Substances

  • Bone Density Conservation Agents
  • Hydroxycholecalciferols
  • Vitamin D
  • Denosumab
  • eldecalcitol
  • alfacalcidol