High-dose vitamin D to attenuate bone loss in patients with prostate cancer on androgen deprivation therapy: A phase 2 RCT.

Charles Kamen, Michelle Janelsins, Charles E Heckler, Chunkit Fung, Karen Mustian, Jennifer E Reschke, Eva Culakova, Luke J Peppone, Supriya Mohile, Amber S Kleckner, Jonathan W Friedberg, J Edward Puzas, Julia Inglis

Journal: Cancer 2024;130(14):2538-2551

PMID: 38520382

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Plain Language Summary

Androgen deprivation therapy (ADT) is a therapy used to inhibit prostate cancer growth, but it may be accompanied by side effects such as loss of bone mineral density (BMD). The aim of this randomised control trial of 52 men aged 60 or over was to determine the effects of high-dose vitamin D on bone health in men with prostate cancer undergoing androgen deprivation therapy ADT.

The results showed that BMD loss at the hip and top of the femur was seen in both groups. However, BMD loss was less in individuals given a vitamin D supplement, especially in individuals with low vitamin D levels. No adverse events or toxicity were reported even at high doses.

It was concluded that high-dose vitamin D may be a feasible and safe option for addressing bone loss in individuals with prostate cancer undergoing ADT and could be considered by healthcare professionals as part of their recommendations for this patient group.

Abstract

BACKGROUND

Androgen deprivation therapy (ADT) inhibits prostate cancer growth. However, ADT causes loss of bone mineral density (BMD) and an increase in fracture risk; effective interventions for ADT-induced bone loss are limited.

METHODS

A phase 2 randomized controlled trial investigated the feasibility, safety, and preliminary efficacy of high-dose weekly vitamin D (HDVD, 50,000 IU/week) versus placebo for 24 weeks in patients with prostate cancer receiving ADT, with all subjects receiving 600 IU/day vitamin D and 1000 mg/day calcium. Participants were ≥60 years (mean years, 67.7), had a serum 25-hydroxyvitamin D level <32 ng/mL, and initiated ADT within the previous 6 months. At baseline and after intervention, dual-energy x-ray absorptiometry was used to assess BMD, and levels of bone cell, bone formation, and resorption were measured.

RESULTS

The HDVD group (N = 29) lost 1.5% BMD at the total hip vs. 4.1% for the low-dose group (N = 30; p = .03) and 1.7% BMD at the femoral neck vs. 4.4% in the low-dose group (p = .06). Stratified analyses showed that, for those with baseline 25-hydroxyvitamin D level <27 ng/mL, the HDVD group lost 2.3% BMD at the total hip vs 7.1% for the low-dose group (p < .01). Those in the HDVD arm showed significant changes in parathyroid hormone (p < .01), osteoprotegerin (p < 0.01), N-terminal telopeptide of type 1 collagen (p < 0.01) and C-terminal telopeptide of type 1 collagen (p < 0.01). No difference in adverse events or toxicity was noted between the groups.

CONCLUSIONS

HDVD supplementation significantly reduced hip and femoral neck BMD loss, especially for patients with low baseline serum 25-hydroxyvitamin D levels, although demonstrating safety and feasibility in prostate cancer patients on ADT.

Address: Department of Surgery, Division of Supportive Care in Cancer, University of Rochester Medical Center, Rochester, New York, USA.; Department of Orthopaedics, University of Rochester Medical Center, Rochester, New York, USA.; School of Nursing, University of Maryland, Baltimore, Maryland, USA.; Department of Medicine, University of Rochester Medical Center, Rochester, New York, USA.; Department of Orthopaedics, University of Rochester Medical Center, Rochester, New York, USA.; Department of Surgery, Division of Supportive Care in Cancer, University of Rochester Medical Center, Rochester, New York, USA.; School of Health Sciences, Liberty University, Charlottesville, Virginia, USA.

DOI: 10.1002/cncr.35275