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Both focal adhesion kinase (FAK) and Pyk2 are implicated in the biology and physiology of bone and cancer.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS.<\/jats:title><jats:p>The efficacy of PF\u2010562,271 was evaluated using MDA\u2010MB\u2010231 cells implanted in the tibia of nude rats. The drug was administered orally at a dose of 5 mg\/kg, 7 days per week for 28 days. Serum and urine biomarkers, imaging, and histologic techniques were deployed to monitor tumor take rate, disease progression, and response to therapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS.<\/jats:title><jats:p>The compound was well tolerated. Both compound\u2010treated groups demonstrated significant and similar increases in osteocalcin and cancellous bone parameters. Radiographic evaluation of tumor\u2010bearing tibiae revealed tumor expansion in nontreated rats compared with a decrease in tumor growth and signs of bone healing in rats treated with PF\u2010562,271. Tartrate\u2010resistant acid phosphatase and fluorescent in situ hybridization analysis revealed that the majority of bone resorption at the tumor site was performed by osteoclasts of rat origin.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS.<\/jats:title><jats:p>The oral administration of PF\u2010562,271 at a dose of 5 mg\/kg suppressed the growth and local spread of intratibial tumors and restored tumor\u2010induced bone loss. The unique ability of PF\u2010562,271 to both curb tumor growth and safely increase bone formation may be an effective therapy for many cancer patients with bone metastases and cancer\u2010associated osteoporosis. 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