This observation was, however, not considered predictive of an increased risk for humans treated for relatively short periods [70]. Baseline values showed that the study population was relatively young (58–59 years old), with relatively elevated spine BMD and low risk T-scores. About 40% of participants had vertebral fractures and half had low free testosterone values. The patterns of biochemical marker changes in response to teriparatide were typical (dose-dependent increases in bone formation and resorption markers) and very closely mirrored similar data in women, albeit with a lower

magnitude [69]. The changes in BMD were also very similar to those previously reported in women [71]. Both teriparatide doses ALK signaling pathway led to the expected changes in spine, total hip and femoral neck BMD. When BMD responses to 20 mcg of teriparatide are compared in men and women, the absolute change in BMD is similar. Analyses showed consistent responses across the risk groups usually seen in male osteoporosis, in that responses did not differ according to baseline BMD, age, gonadal status, previous fracture status, smoking or alcohol consumption [69]. In an 18-month follow-up study, about 80% of patients agreed to be observed without receiving study medication, but with the option to undertake other therapies [72]. After treatment discontinuation, BMD declined in both teriparatide treatment

groups, particularly at the lumbar spine [72]. There was no difference in the rate of BMD decline as a function of testosterone concentrations [72]. From MLN0128 the original treatment trial baseline to the 18 months visit of the follow-up study, there was a lower incidence of moderate and severe fractures, in the combined 20 and 40 mcg teriparatide groups than in the placebo group (p = 0.01)

[72]. However, these data should be interpreted with caution, because approximately 22% of the men reported the use of a bisphosphonate at some point during the follow-up study. Again, the point estimates for the reduction in Nabilone vertebral fracture risk in men were essentially the same as in women [73], despite the smaller study size. Of interest, Leder et al. investigated the effects of teriparatide treatment and discontinuation [74] in a small study involving 14 postmenopausal women and 17 eugonadal men with osteoporosis, aged 46–85 years, with lumbar spine or femoral neck T-scores <− 2 SD. Daily teriparatide (37 mcg) was administered subcutaneously for 24 months, followed by 12 months off therapy. The study observed that, following teriparatide discontinuation, the rate of BMD decline was greater in women than in men, possibly highlighting a difference in teriparatide response or in the drivers of BMD maintenance in men and women. The 5.9% female to male difference in trabecular BMD loss was statistically significant (p = 0.037; 95% CI, 11.2–0.