Prevalent and Emerging Therapies for Osteoporosis

Abstract

Osteoporosis and fractures associated with it constitute a real and serious socio-medical problem, which only recently has come to the forefront of social consciousness. With increasing number of exservicemen and their dependents, osteoporosis management has become very important in our setup. Currently available pharmacological therapies for prevention of fragility fractures are limited in scope, efficacy and acceptability to patients. Oral bisphosphonates are the standard treatment for osteoporosis which are associated with significant gastrointestinal side effects and thus poor patient compliance. Newer regimens, including intravenous (IV) formulations of bisphosphonates, have successfully come in vogue with greater patient compliance and equal or better benefits. The real need in osteoporosis treatment is for additional anabolic drugs. The only currently approved anabolic agent for treating osteoporosis is teriparatide (recombinant human parathyroid hormone 1-34), which stimulates new bone formation. Considerable efforts are being made to develop new, more effective treatment for osteoporosis. These novel drugs under trial include those primarily inhibiting osteoclastic bone resorption (like bisphosphonates) such as inhibitors of receptor activator of nuclear factor-kappa B ligand (RANKL) signalling, cathepsin K inhibitors, c-Src kinase inhibitors, integrin inhibitors, chloride channel inhibitors and the drugs with osteo-anabolic actions such as orally active parathyroid hormone (PTH) analogues, calcium sensing receptor antagonists, PTH-related peptide analogues and agents that induce osteoblast anabolism via pathways involving key, recently identified, molecular targets (wnt low-density lipoprotein receptor-related protein-5 signalling; sclerostin antibodies). MJAFI 2010; 66 : 249-254Key Words : Osteoporosis; Prevalent; Emerging therapies MJAFI, Vol. 66, No. 3, 2010 250 Brar the incidence of fractures, particularly in population likely to have deficient intake or limited sun exposure. In these patients supplementation with vitamin D can be achieved equally well with daily, weekly or monthly dosing [2]. BisphosphonatesBisphosphonates are pyrophosphate analogues that bind to bone minerasl are then taken up by osteoclasts and rapidly inhibit bone resorption. Alendronate and risedronate are approved for prevention and treatment of osteoporosis on the basis of evidence that they decrease bone resorption, increase bone mass in the spine and hip and decrease the incidence of fractures. Bisphosphonates can prevent bone loss in patients receiving glucocorticoids and in osteoporotic men. There is no consensus on the duration of therapy, but continued benefit has been observed in patients treated for upto 10 years [3]. Bisphosphonates are poorly absorbed orally and must be taken on an empty stomach with no food or other medication. Their gastrointestinal side effects may be reduced by giving bisphosphonates weekly instead of daily. This problem may be circumvented by using parenteral bisphosphonates. Hormon...

Dose‐response effects of exercise on bone mineral density and content in post‐menopausal women

“…The adherence to the intervention was monitored by weekly exercise logs that were completed by the participants and verified by the trainers. These logs included information on the exercise time spent in the prescribed heart rate zones and the rate of perceived exertion (Borg scale, [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. Subsequently, there was no intervention during the 12-month follow-up period.…”

“…Several lifestyle and pharmacologic interventions to prevent the loss of bone mineral density in women have been assessed within randomized settings . Pharmacological treatments, such as the prescription of bone resorption inhibitors or bone formation stimulators, are widely used in post‐menopausal osteoporosis to help maintain bone mineral density . However, the widespread and long‐term use of these drugs is limited because of possible side effects (eg, fever, nausea, muscle and bone pain, toxicity, heart disease, and cancer) …”

RANKL/RANK/OPG Pathway: A Mechanism Involved in Exercise-Induced Bone Remodeling

“…For example, physical activity, healthy diets, and medical intervention can help the prevention of agerelated bone loss or osteoporosis [18]. Several medications like bone resorption inhibitors and bone formation stimulators are in a postmenopausal treatment lineup [23]. ese include bisphosphonates (e.g., alendronate) [24], strontium ranelate [25], denosumab (RANKL inhibitor) [26], and PTH [27].…”

Cross sectional study of osteoporosis among women

“…The benefits of the three components of non-pharmacological therapy are well established which includes diet, regular weight bearing exercises and cessation of smoking & alcohol consumption. 3,4 Measuring the bone mineral density (BMD) remains the only important tool in the early diagnosis of osteoporosis, so that effective preventive and therapeutic measures can be initiated at the earliest. The gold standard for measuring bone density however is Dual Energy X-ray Absorptiometry (DEXA), useful tool for both axial and appendicular skeleton.…”