Bone protecting agents

Endocrine therapies that lower circulating estradiol, activate osteoclasts and lead to increase bone resorption and reduced bone formation.

Bone targeted, therapies inhibit osteoclast function and can restore balance in bone physiology, helping to improve bone health and reduce detrimental clinical side effects, including fractures.

The anti-cancer activity of anti-resorptive agents is an indirect effect of the agents on the bone/bone marrow microenvironment.

In addition to inhibiting osteoclasts bisphosphonates and denosumab promote the immobilization of dormant cancer stem cells in the  bone marrow.

For men with asymptomatic or mildly symptomatic mCRPC, using bone-protecting agents during treatment with radium-223 plus enzalutamide controlled the risk for fractures.

In the randomized phase 3 EORTC-1333-GUCG/Peace-3 trial investigators randomized patients 1:1 to receive either enzalutamide at 160 mg daily plus radium-223 at 55 kBq/kg every 4 weeks for 6 cycles, or enzalutamide alone.

Radiographic progression-free survival served as the primary end point.

It was made mandatory to use a bone-protecting agent in all patients for at least 6 weeks before starting radium-223. 

Before administering the safety letter, 45.2% of patients had not received a BPA, compared with just 3% who had not after the letter was sent out.

The cumulative incidence of fractures at 1 year was 37.1%, in the combination arm and 15.6% in the enzalutamide alone arm. 

In men who received a BPA, the 1-year incidence of fractures was reduced to 2.7% and 2.6%, respectively.

At 18 months, the cumulative incidence was 45.9% in the combination arm and 21.9% in the enzalutamide alone arm, without a BPA. 

With a BPA, the incidence was 4.3% and 2.6%, respectively.

Radium-223 is an alpha-emitting radiopharmaceutical that has demonstrated an overall survival benefit in men with mCRPC.

In the randomized, double-blind, placebo-controlled ERA223 trial, investigators evaluated the use of concurrent treatment with abiraterone acetate (Zytiga; 1000 mg once daily) plus prednisone (5 mg twice daily) or prednisolone (5 mg twice daily) and radium-223 (55 kBq/kg) in 806 patients with mCRPC: BPAs significantly reduced the rate of fractures in both treatment arms.

Treatment with androgen-deprivation therapy (ADT)] can induce bone loss. 

Bone protecting agents can also delay the time to a first skeletal-related event [SRE] in men with castration-resistant prostate cancer and bone metastasis.

Anti-resorptive agents, such as zoledronic and denosumab are approved for the management of metastatic bone disease in patients with solid tumors and reduce the development of skeletal  related events.

Anti-resorptive agents are prescribed for the prevention of bone loss and/or fragility fractures associated with androgen deprivation therapy for prostate cancer and endocrine therapy for breast cancer.

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