Managing Bone Loss in Men With Locally Advanced Prostate Cancer Receiving Androgen Deprivation Therapy

Purpose

We reviewed the pathogenesis, diagnosis, prevalence, prevention and treatment of bone loss in patients with nonmetastatic prostate cancer receiving androgen deprivation therapy.

Materials and Methods

Using PubMed® we performed a comprehensive literature search to identify articles on bone mineral density loss in patients with nonmetastatic prostate cancer receiving androgen deprivation therapy. Pertinent articles were reviewed and evaluated.

Results

Bone mineral density loss and related fractures were recently established as significant adverse events associated with androgen deprivation therapy. Patients with nonmetastatic prostate cancer receiving androgen deprivation therapy experience annual bone mineral density losses of 0.6% to 4.6% with the most significant loss within year 1 of therapy. In addition to calcium and vitamin D supplements, current treatment options for androgen deprivation therapy induced bone loss include synthetic estrogens, selective estrogen receptor modulators and bisphosphonates. Recent safety concerns have been identified, including renal dysfunction with intravenous bisphosphonates and osteonecrosis of the jaw with oral and intravenous bisphosphonates. However, minimal renal dysfunction and no cases of osteonecrosis of the jaw have been reported in this setting.

Conclusions

Because the most significant bone mineral density loss occurs within year 1 of androgen deprivation therapy and most fractures in healthy men occur in those without osteoporosis, early intervention is warranted to prevent skeletal morbidity in patients with nonmetastatic prostate cancer receiving androgen deprivation therapy. Although the majority of and the most compelling evidence supports the use of bisphosphonates for preventing and treating androgen deprivation therapy induced bone loss, further study is needed to define the optimal regimen, timing of initiation and duration of therapy as well as long-term efficacy and safety.

Key Words: prostate, bone and bones, prostatic neoplasms, androgen antagonists, osteoporosis

Abbreviations and Acronyms: ADT, androgen deprivation therapy, AE, adverse effect, BMD, bone mineral density, BMI, body mass index, BSAP, bone-specific alkaline phosphatase, DES, diethylstilbestrol, DEXA, dual energy x-ray absorptiometry, FN, femoral neck, LHRH, luteinizing hormone-releasing hormone, LS, lumbar spine, NR, not reported, NTx, N-telopeptide, ONJ, osteonecrosis of jaw, PC, prostate cancer, SERM, selective estrogen receptor modulator, TH, total hip, VitD, vitamin D