POS1105 EFFECTS OF CHOLECALCIFEROL AND CALCIFEDIOL IN OSTEOPOROTIC WOMEN WITH SECONDARY HYPERPARATHYROIDISM DUE TO SEVERE VITAMIN D DEFICIENCY UNDERGOING ZOLEDRONIC ACID TREATMENT: A RANDOMIZED-CONTROLLED TRIAL

Background:Secondary hyperparathyroidism (sHPTH) due to vitamin D deficiency impairs the bone mineral density (BMD) response to alendronate,1-2 but the optimal strategy for its correction in postmenopausal osteoporotic women (PMO) about to start zoledronic acid (ZOL) therapy is still unknown.Objectives:To evaluate the effects of cholecalciferol (D3) and calcifediol (25OHD) on serum 25-OH-vitamin D (s25OHD), parathyroid hormone (PTH) and BMD in PMO presenting with sHPTH due to vitamin D deficiency.Methods:PMO with s25OHD <20 ng/ml, sHPTH (PTH >65 pg/ml) and BMD T-score at the lumbar spine (LS), femoral neck (FN) or total hip (TH) < -2.5, or between -1 and -2.5 plus one vertebral/femoral fracture, were randomly assigned to receive a therapeutic dose of D3 (300.000 IU bolus) followed by 175 mcg/weekly of D3, or 175 mcg/weekly of 25OHD alone, 2 months before receiving a single intravenous infusion of ZOL (5 mg). BMD at the LS, FN and TH was assessed at baseline and after one year from ZOL. Serum calcium, PTH and s25OHD were measured at baseline, and 6- and 12-month after ZOL. Adverse and clinical events were ascertained by 3-and 9-month telephone interviews, and by 6- and 12-month clinical evaluation.Results:45 PMO (25OHD N=23, D3 N=22) were enrolled over one year and 32 subjects (mean age ±SD 75±10 years, range 51-91) completed the 1-year of treatment/follow-up (25OHD N=17, D3 N=15). Most PMO discontinued for protocol violation, while three deceased before study ending (25OHD N=1, D3 N=2) for reasons not related to the agents investigated. The baseline characteristics were comparable in both groups. At baseline mean s25OHD (±SE) was 8±1 ng/ml in the 25OHD group and 8±1 ng/ml in the D3 group. The corresponding figures for PTH were 111±6 pg/ml (25OHD) and 117±5 pg/ml (D3). Mean s25OHD (±SE) increased in both groups at 6- and 12-month, being significantly greater in the 25OHD group (12-month, 56±2 ng/ml) compared to the D3 group (12-month, 34±2 ng/ml, P<.001) at both time points (Figure 1). PTH (mean ±SE) decreased in both groups, being significantly lower in the 25OHD group at 12-month (25OHD 46±6 pg/ml versus D3 70±6 pg/ml, P=.007), as shown in Figure 1. BMD at the LS, FN and TH increased in both groups (with significant increases versus baseline only at the FN) without significant differences between s25OHD and D3. In PMO receiving D3 serum calcium remained stable over time, while those receiving s25OHD demonstrated a significant increase of serum calcium, with 2 PMO presenting a value close to the upper limit of the reference range at 12-month. No patient reported incident fractures or adverse events.Conclusion:Calcifediol 175 mcg weekly appears more potent in improving s25OHD and decreasing PTH concentrations compared to cholecalciferol therapeutic dose (300’000 IU) plus 175 mcg weekly in PMO presenting with sHPTH due to severe vitamin D deficiency about to start ZOL therapy. Further studies are warranted to clarify implications on BMD improvements on the long-term of similar 25OHD and D3 regimens.References:[1]Barone A et al., J Am Geriatr Soc 2007.[2]Kincse G et al., BMC Musculoskelet Disord 2012.Disclosure of Interests:Giulia Botticella: None declared, Monica Pizzonia: None declared, Barbara Cossu: None declared, Roberta Bruno: None declared, Dario Camellino Speakers bureau: AbbVie, Celgene, Janssen-Cilag, Eli Lilly, Medac, Mylan, Novartis, and Sanofi, outside the submitted work, Giuseppe Girasole Speakers bureau: Abiogen Pharma and Novartis, outside the submitted work, Andrea Giusti Speakers bureau: UCB, Amgen, Kyowa Kirin, Abiogen Pharma, and Eli Lilly, outside the submitted work, Consultant of: EffRx and Abiogen Pharma, outside the submitted work, Mario Pedrazzoni: None declared, Simona Alexovits: None declared, Franco Pleitavino: None declared, Federico Santolini: None declared, Alessio Nencioni: None declared, Gerolamo Bianchi Speakers bureau: Abbvie, Abiogen Pharma, Amgen, BMS, Celgene, Eli Lilly, GSK, Janssen-Cilag, Medac, MSD, Novartis, Pfizer, Roche, Sanofi, Genzyme, and Servier, outside the submitted work.