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

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• Androgen deprivation therapy can affect bone health in men with PCa.

• Vitamin D may be necessary to support healthy bones during ADT.

• Consider high dose Vitamin D therapy at 50,000 IU/week under the guidance of a medical professional, especially in those with low serum 25-hydroxyvitamin D levels <32 ng/ml.

• Ensure that bone health is monitored if undergoing ADT.

Introduction -

Androgen deprivation therapy (ADT) is a treatment that is growing in use for prostate cancer (PCa). However, one of the side effects of ADT is loss of bone mineral density, which may further exacerbate bone loss typically experienced as part of the disease process of PCa. Vitamin D and calcium supplementation are currently recommended for all individuals undergoing ADT and high dose vitamin D (HDVD) is a promising therapy to prevent bone loss. This study aimed to determine the efficacy, safety and feasibility of HDVD for the prevention of bone mineral density (BMD) loss compared to guideline vitamin D administration.

Methods -

This was a Phase 2 randomised control trial and pariticpants were randomly allocated to two groups HDVD: vitamin D (50,000 IU/week)+ multivitamin+calcium vs placebo: vitamin D (800IU/week)+multivitamin+calcium, over a 24 week trial period.

• 52 individuals aged 60 or over with PCa undergoing ADT completed the trial.

• Outcomes were BMD of the lumbar spine, femoral neck, and total hip measured by dual energy x-ray absorptiometry scan.

• Serum vitamin D, calcium, and bone metabolism biomarkers were assessed via a fasting blood draw.

Results -

• Serum vitamin D levels rose considerably in the HDVD group compared to placebo.

• No differences were seen between the two groups in serum calcium levels.

• HDVD was associated with mitigation of BMD loss of the total hip (high-dose: −1.5% vs placebo: −4.1%; Cohen’s = 0.23; p= .03) and femoral neck (high-dose: −1.7% vs placebo: −4.4%; Cohen’s = 0.22; p = .06) compared to placebo.

• The HDVD group lost slightly more BMD in the total spine compared with placebo, but the difference was not significant (high-dose: −1.2% vs placebo: −0.5%; P=0.56).

• When individuals were stratified based on baseline 25(OH)D levels, those with lower levels given HDVD were associated with greater mitigation of bone loss of the total hip (high-dose: −2.3% vs placebo: −7.1%; Cohen’s = 0.42; p < .01) and femoral neck (high-dose: −2.2% vs placebo: −8.0%; Cohen’s = 0.43; p= .03).

• Some of the bone biomarkers were not statistically different between the groups except for the bone resorption markers c-terminal telopeptide (CTX) and n-terminal telopeptide (NTX), which increased in the HDVD group (P=0.02 and P=0.01 respectively).

Conclusion -

HDVD was safe and effective at preventing BMD loss at the hip and femoral neck of older men receiving ADT for PCa, especially in those with lower baseline serum 25(OH)D levels.

• Individuals who may get the most benefit from HDVD may be those with lower baseline serum 25(OH)D levels. Assessing 25(OH)D levels before initiating ADT may determine who may benefit the most.

• Ensure adequate calcium and vitamin D during treatment and consider HDVD in high risk individuals.

• Monitor bone health in those undergoing ADV for PCa.

• Larger, longer-duration trials are needed to determine whether the benefits of high-dose vitamin D on bone mineral density are sustained beyond 24 weeks and translate into reductions in fracture risk.

• Studies need to identify optimal doses.

• Investigate underlying mechanisms. Despite improvements in BMD, bone resorption markers increased with HDVD. Further studies are needed to clarify the biological mechanisms responsible for these findings.