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In the last few years, much progress has been achieved in the discovery of new drug target sites for treatment of osteoporotic disorders, one of the main challenging diseases with a large burden for the public health systems. Among these new agents promoting bone formation, shifting the impaired equilibrium between bone anabolism and bone catabolism in the direction of bone synthesis are inorganic polymers, in particular inorganic polyphosphates that show strong stimulatory effects on the expression of bone anabolic marker proteins and hydroxyapatite formation. The bone-forming activity of these polymers can even be enhanced by combination with certain small molecules like quercetin, or if given as functionally active particles with certain divalent cations like strontium ions even showing by itself biological activity. This chapter summarizes recent developments in the search and development of novel anti-osteoporotic agents, with a particular focus on therapeutic approaches based on the potential application of inorganic polymers and combinations.

One of the most frequent, but also most undiagnosed, endocrinopathies is male hypogonadism (testosterone deficiency). Understanding the variety of clinical pictures male hypogonadism exhibits is pivotal for diagnosis and putative treatment. There can be disturbances of mood and cognitive abilities as well as sexual functions. Further on, a decrease in muscle mass and strength, an accumulation of body fat and osteopenia/osteoporosis as well as anemia might be observed. There are indications that insulin sensitivity is mitigated in a state of androgen depletion, especially due to an inverse association of testosterone to the metabolic syndrome. In older men, symptoms of androgen deficiency may feature a differential profile due to accompanying co-morbidities. Restoring serum testosterone levels by substitution therapy can markedly attenuate, if not relieve, the clinical picture of hypogonadism. New treatment modalities have been introduced, including short-acting transdermal as well as long-acting depot preparations. Herewith, the diagnostic pathways to describe or exclude male hypogonadism and as well as various options of initiation and surveillance of testosterone substitution therapy are elucidated. Future perspectives of andrology regarding metabolic and pharmacogenetic aspects are discussed.

Patients with adult growth hormone deficiency apparently can develop a clinical picture with pronounced obesity, dyslipidemia, decreased bone density, and increased fracture rate as well as psychosocial limitations irrespective of the loss and replacement of further hypophyseal axes. The extent of these changes is strongly dependent on interindividual variations. Retrospective analyses have indicated a possibility of elevated morbidity and mortality among this patient cohort which can be due to the proatherogenic alterations (central obesity, dyslipidemia). Treatment with recombinant growth hormone in controlled trials resulted in evident improvement in quality of life, better body composition and lipid profile as well as an increase in bone density. Whether these improvements will also pay off in terms of reduction of endpoints (decline in fracture rates, decrease of cardiovascular morbidity and mortality) has not yet been confirmed by controlled studies. When administered at low doses, titrated according to the IGF-1 level, growth hormone replacement appears to be a safe and well-tolerated therapeutic regimen.

Replacement with adrenal steroids comprises treatment with glucocorticoids, mineralocorticoids and adrenal androgen precursors, mainly in patients with adrenal insufficiency. Attention has also been directed to replacement treatment with glucocorticoids in critically ill patients or with dehydroepiandrosterone (DHEA) in elderly people with an age related decline of DHEA/DHEAS levels. Despite the use of current replacement concepts well-being is often not fully restored in patients with adrenal insufficiency. Innovations comprise the development of new delayed release glucocorticoid preparations that allow to better mimic the circadian cortisol secretion and may have the potential to improve the treatment of patients with adrenal insufficiency. Recent results from the CORTICUS study have not confirmed previous beneficial results and have led to restrictions in the use of hydrocortisone substitution therapy in patients with septic shock. Treatment with the androgen precursor DHEA in patients with adrenal insufficiency may improve quality of life. However, in patients with an age related decline of DHEA levels, the available evidence does not support the use of DHEA replacement as an anti aging treatment.