Therapeutic options for treatment of osteoporosis-related fractures in males; a novel strategy for treatment of osteoporosis using new selective androgen receptor modulators (SARMs)

• Applicants: Dr. Marina Komrakova; Professor Dr. Stephan Sehmisch
• Subject Area: Orthopaedics, Traumatology, Reconstructive Surgery
• Term: from 2014 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 261336384

The incidence of osteoporosis and osteoporosis-related fractures is predicted to be increased dramatically in the coming years. In contrast to the male osteoporosis, diagnosis and treatment of postmenopausal osteoporosis in women has been the main focus of the research. Despite increasing recognition of the problem of male osteoporosis, the considerable gap remains in the knowledge regarding this disorder and its treatment. There are few treatments of osteoporosis in men, bisphosphonates, human parathyroid hormone (PTH), strontium ranelate (SR) and denosumab. All these drugs affect predominantly bone tissue having no or little effect on muscle tissue. Until the onset of the first fractures, osteoporosis is clinically silent. Diagnosis of osteoporosis is often done after a fracture occurs. The approved treatments for osteoporosis are not prescribed during fracture healing because it is supported that anti-osteoporosis agents could affect bone healing processes. Currently, non-steroidal selective androgen receptor modulators (SARMs) are being developing. Two compounds ostarine and BMS-564929 will be studied. Ostarine increases the lean body mass and physical performance in patients of both sexes affected by cancer cachexia. BMS-564929 has been developed for the treatment of symptoms of age-related decline in androgen levels in men. Studies regarding bone tissue and fracture healing have been not reported so far.In the proposed study, the effect of SARMs on intact bone and fracture healing will be studiedIn the first part, the metaphyseal osteotomy of tibia with T-plate osteosynthesis will be created in orchiectomized rats. SARMs and testosterone will be applied as osteoporosis therapy or prophylaxis to study bone healing and muscle function.Estrogen and testosterone are important for the prevention of bone and muscle loss in men. However, they are not applied because of the negative side effects. Due to the interaction between estrogens and androgens in bone and muscle metabolism, synergistic effects of SERMs and SARMs could be possible. In Part 2, the replacement of testosterone and estrogen with selective receptor modulators (SERM or/and SARM) will be studied in rats. Orchiectomized rats will develop osteoporosis, and then will be treated with substances prior to the tibia osteotomy and during bone healing period. The results will provide a new knowledge regarding osteoporosis as well as its treatment in men. A novel strategy for the treatment of osteoporosis using new SARMs will be evaluated in males. The findings of the proposed studies may show up a new perspective for therapeutic treatment of osteoporosis and osteoporosis-related fractures.

• DFG Programme: Research Grants
• Participating Persons: Privatdozent Dr. Christian Dullin; Dr. Ulrich Schmelz; Professor Dr. Klaus Michael Stürmer; Professor Dr. Michael Wicke (†)