|dc.description.abstracteng||Osteoporosis is the most common generalized bone disease. About 200 million people are affected worldwide. It is a multifactorial disease, the central problem of which are fractures, which can occur as a result of the decrease in bone mineral density and the disturbed microarchitecture, and which are accompanied by chronic pain and sometimes severe limitations in quality of life.
After years of assuming that osteoporosis mainly affects women, osteoporosis in men has increasingly become the focus of scientific attention in recent years. The most common cause of the development of osteoporosis in men is hypogonadism, which is accompanied by a decrease in testosterone levels. This can occur, among other things, due to inflammation, tumors, injuries in younger men (< 40 years) or in men after castration (indicated e.g. in the case of prostate or testicular carcinoma), but even more frequently in older men (> 40 years) in the form of age hypogonadism.
In the specific treatment of osteoporosis in men, PTH is a further therapeutic agent in addition to bisphosphonates, denosumab, strontium ranelate and hormone replacement therapy. Due to the antiosteoporotic effect of the parathyroid hormone on bone, it was approved in Germany in 2003 for the treatment of postmenopausal osteoporosis and, in June 2007, for the treatment of osteoporosis in men at high risk of fracture (Lilly press release 2008). Experience has shown that different anti-osteoporosis drugs can have different effects and intensities of action on different skeletal areas (vertebral body, femoral neck, radius, calcaneus, etc.). It is therefore appropriate to investigate these possible differences also in PTH (Woratanarat et al. 2009; Tezval et al. 2010).
Since the most common fracture in men with existing osteoporosis is the fracture of the trochanteric region, this study focuses on the skeletal region. The aim was to investigate the effect of intermittent application of PTH on the strength, microarchitecture and bone mineral density of the trochanteric region of orchiectomized rats and to observe in which bone layer, endosteal or periosteal, PTH exerts its main effect.
The present study used 72 rats, 48 of which were orchiectomized and 24 sham-operated. The animals were divided into four groups, with two groups orchiectomized and the other two sham-operated. One half of the population received intermittent daily PTH (40 µg/kgKG) and the other half a placebo (0.9% NaCl) at the same injection times. The four groups were fed soy-free feed for the entire trial period of 17 weeks. The feed consumption and the body weight of the animals were weighed weekly. The development of osteoporosis was induced by orchiectomy in the respective groups. Twelve weeks later osteotomy was performed in all animals in the proximal tibiametaphysis area. After osteotomy, group-specific daily intermittent PTH or placebo application was performed for 5 weeks. In addition, polychrome sequence marking of the test animals was carried out according to a defined scheme to identify regions of new bone formation. 17 weeks after the start of the experiment, the animals were autopsied. The effect of the intermittent application of PTH was then investigated using biomechanical, histomorphometric, fluorescence microscopic and mineral content determination methods.
The results show that intermittent parathyroid hormone application counteracts hypogonadism induced bone loss in the trochanteric region of the rat femora. After daily therapy with PTH, an increase in mechanical bone strength, trabecular microarchitecture and bone mineral content of the femora was observed in both osteoporotic (Orx + PTH) and, to a lesser extent, healthy animals (Sham + PTH). Especially in osteoporotic bone, a significant increase in the density of trabecular crossings was also detected. Furthermore, an increase in the B.Dm./Ma.Dm.-ratio was observed, which describes the relative increase in thickness of the cortical bone. By fluorescence microscopic evaluation of the cross sections of the trochanteric region of the rat femora it could be shown that PTH activates in particular the formation of new bone in the endosteal cortex, while the periosteal cortical surface was only minimally affected. In this study, PTH had no influence on weight and feed intake.
Since the positive effect of PTH on bone could be demonstrated in both orchiectomized osteoporotic (Orx + PTH) and non-osteoporotic animals (Sham + PTH), it can be summarized that intermittent application of PTH is an alternative not only for the therapy but also for the prophylaxis and prevention of hypogonadal male osteoporosis.
Especially in hypogonadism induced osteoporosis in men or diseases where testosterone replacement therapy is contraindicated, such as prostate cancer or benign prostate hyperplasia, PTH therapy can be a beneficial alternative.||de