The effects of high-dose calcitriol and individualized exercise on bone metabolism in breast cancer survivors on hormonal therapy: a phase II feasibility trial
Cancer treatment-induced bone loss (CTIBL) is a long-term side effect of breast cancer therapy. Both calcitriol and weight-bearing exercise improve bone metabolism for osteoporotic patients, but are unproven in a breast cancer population. We used a novel high-dose calcitriol regimen with an individualized exercise intervention to improve bone metabolism in breast cancer survivors.
We accrued 41 subjects to this open label, 2 × 2 factorial, randomized feasibility trial. Breast cancer survivors were randomized to receive the following: (1) calcitriol (45 micrograms/week), (2) individualized exercise with progressive walking and resistance training, (3) both, or (4) a daily multivitamin (control condition) for 12 weeks. Primary outcomes included changes in biomarkers of bone formation, bone resorption, and the bone remodeling index, a composite measure of bone formation and resorption. Safety measures included clinical and biochemical adverse events. A main effect analysis was used for these endpoints.
Hypercalcemia was limited to three grade I cases with no grade ≥ 2 cases. Among exercisers, 100% engaged in the prescribed aerobic training and 44.4% engaged in the prescribed resistance training. Calcitriol significantly improved bone formation (Cohen’s d = 0.64; p < 0.01), resulting in a non-significant increase in the bone remodeling index (Cohen’s d = 0.21; p = 31). Exercise failed to improve any of the bone biomarkers.
Both calcitriol and exercise were shown to be feasible and well tolerated. Calcitriol significantly improved bone formation, resulting in a net increase of bone metabolism. Compliance with the exercise intervention was sub-optimal, which may have led to a lack of effect of exercise on bone metabolism.
KeywordsCalcitriol Exercise Breast cancer Hormonal therapy Bone metabolism Bone health
Compliance with ethical standards
This study was reviewed and approved by the URMC Research Subjects Review Board (RSRB). All research participants gave written informed consent.
Conflicts of interest
The authors declare that they have no conflicts of interest.
- 2.American College of Sports Medicine, Thompson WR, Gordon NF, Pescatello LS (2010) ACSM's guidelines for exercise testing and prescription. Lippincott Williams & Wilkins, PhiladelphiaGoogle Scholar
- 3.Avenell A, Mak JC, O'Connell D (2014) Vitamin D and vitamin D analogues for preventing fractures in post-menopausal women and older men the Cochrane database of systematic reviews: Cd000227Google Scholar
- 8.Beer TM, Ryan CW, Venner PM, Petrylak DP, Chatta GS, Ruether JD, Chi KN, Young J, Henner WD (2008) Intermittent chemotherapy in patients with metastatic androgen-independent prostate cancer: results from ASCENT, a double-blinded, randomized comparison of high-dose calcitriol plus docetaxel with placebo plus docetaxel. Cancer 112:326–330CrossRefPubMedGoogle Scholar
- 24.Hirbe A, Morgan EA, Uluckan O, Weilbaecher K (2006) Skeletal complications of breast cancer therapies clinical cancer research : an official journal of the American Association for Cancer Research 12: 6309s-6314sGoogle Scholar
- 25.Kamen C, Heckler C, Janelsins MC, Peppone LJ, McMahon JM, Morrow GR, Bowen D, Mustian K (2015) A dyadic exercise intervention to reduce psychological distress among lesbian, Gay, and Heterosexual Cancer Survivors LGBT healthGoogle Scholar
- 27.Kleckner IR, Kamen C, Gewandter JS, Mohile NA, Heckler CE, Culakova E, Fung C, Janelsins MC, Asare M, Lin PJ, Reddy PS, Giguere J, Berenberg J, Kesler SR, Mustian KM (2017) Effects of exercise during chemotherapy on chemotherapy-induced peripheral neuropathy: a multicenter, randomized controlled trial supportive care in cancer : official journal of the multinational Association of Supportive Care in cancerGoogle Scholar
- 40.Vasikaran S, Eastell R, Bruyere O, Foldes AJ, Garnero P, Griesmacher A, McClung M, Morris HA, Silverman S, Trenti T, Wahl DA, Cooper C, Kanis JA (2011) Markers of bone turnover for the prediction of fracture risk and monitoring of osteoporosis treatment: a need for international reference standards. Osteoporos Int 22:391–420CrossRefPubMedGoogle Scholar