The aim of this clinical investigation was to assess the physical performance in osteoporotic patients undergoing drug treatment (DT) for years by measuring hand grip strength (HGS) and bone mineral density (BMD). Afurther aim was to detect the time until the occurrence of vertebral fractures (VF) and influencing factors. The investigation comprised 346 persons (276women, 70men) aged on average 66.9 ± 10.7years with confirmed osteoporosis (OP). Over amean period of 1384 ± 727days, OP was assessed every 2 years, including abone densitometry by dual X‑ray absorptiometry and HGS measurement. In subgroups OP patients were analyzed with and without abone density (BMD) increase, and with and without VFs. Under DT, calcium and vitaminD substitution, the median T‑score improved in the entire group from -3.2 to -3.1 standard deviations (SD; p = 0.002). HGS was reduced (median) from 26 kg to 24 kg (p < 0.001). The median interval until the occurrence of VF was 2652days (95% confidence interval [CI] 1825.2-3478.8days) and 1461days (95% CI 1246.5-1675.5, p < 0.001) in those with and without aBMD increase, respectively. Guideline-based DT improves bone density and causes alonger interval without VF. The HGS falls independent of BMD. The association between bone and muscle in patients with adeterioration of the musculoskeletal system is known as osteosarcopenia. Early muscle exercises would be meaningful in this setting.