Organic nitrates for osteoporosis: an update

Abstract

The number of osteoporotic fractures is increasing worldwide as populations age. An inexpensive and widely available treatment is necessary to alleviate this increase in fractures. Current treatments decrease fractures at trabecular bone sites (spine) but have limited effects at cortical sites (hip, legs, forearm and upper arm)-the most common sites of osteoporotic fracture. Treatments are also limited by costs, side effects and lack of availability. Nitric oxide (NO) is a novel agent that has the potential to influence cortical bone, is inexpensive, widely available and has limited side effects. In this review, we will evaluate the in vitro and in vivo data that support the concept that NO is important in bone cell function, review the observational, case control and randomized trial data on organic nitrates and the effects of these agents on bone turnover, geometry and strength.

Figure 1

The L-arginine-nitric oxide (NO) pathway. Endogenous NO is synthesized from L-arginine and molecular oxygen by the nitric oxide synthase (NOS) group of enzymes and reacts rapidly with oxygen to form nitrate (NO₃) and nitrite (NO₂). Exogenous sources of NO can be supplied via NO donors such as isosorbide mononitrate, isosorbide dinitrate and nitroglycerin.