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Osteoporosis is known to increase in prevalence with age. With aging of population in the recent years, the number of male osteoporosis patients is increasing. Osteoporosis can progress without symptoms. Diagnosis and treatment of osteoporosis are often delayed especially in men, because the concept of male osteoporosis has not been fully penetrated. Even after fragile fracture caused by osteoporosis, it is frequent that an appropriate treatment for osteoporosis has not been provided in men. Furthermore, it has been reported that about half of male osteoporosis patients have secondary causes. In management of osteoporosis patients, we have to pay attention to background diseases and life style of the patients.

Both androgen and estrogen play important roles in bone metabolism. As estrogen has a potent inhibitory effect on bone resorption, bone turnover increases in postmenopausal osteoprosis caused by estrogen deficiency. Treatment with selective estrogen receptor modulator (SERM) as well as hormone replacement therapy (HRT) improve bone turnover increased in postmenopausal women to normal range before menopause. Although the decrease of androgen level with aging is involved in pathogenesis of male osteoporosis, the detailed mechanism remains to be clarified.

DHEA is the major source for estrogen biosynthesis in postmenopausal women, since DHEA is converted to estrogen by aromatase in peripheral tissues. It has been suggested by animal models that a direct action of DHEA on bone tissue exists in addition to a biological action by estradiol converted from DHEA. Several RCTs (randomized, double-blinded, controlled trials) indicated that administration of daily 50 mg of DHEA increased bone mineral density (BMD) of lumbar spine or femoral neck. Increment of BMD was significant but small. The effect of DHEA on BMD is considered to be attributable to that of estradiol converted from DHEA, judging from analysis of serum steroid hormone concentrations.

Androgen inhibits osteoclastic bone resorption with increase of bone formation through androgen receptor in bone tissue. Anabolic steroids are synthetic derivates of testoterone. Anobolic steroids have favorable anabolic actions, lessening virilizing effects. Several anabolic steroids have been synthesized and some of them have been approved as a drug for anti osteoporosis. Anabolic steroids have revealed the increased bone mineral content or bone mineral density at the radius, and the lumbar spine in osteoporosis patients. Anabolic steroids have also decreased fat mass with increase of lean body mass and muscle mass, and lessened bone pain in osteoporosis patients having bone fracture, which seem to be favorable effects for especially elder osteoporosis patients. But in recent years the number of osteoporosis patients treated with anabolic steroids has been decreasing. Furthermore recently few clinical trials about the effect of anabolic steroids on osteoporosis have been reported, and prospective study for bone fracture using anabolic steroids has not reported yet. We would like to expect additional effects except on bone formation will enhance the frequency in use of anabolic steroids, and the prospective clinical study about the prevention against bone fracture will be reported in the future.

Direct inhibitory effect of glucocorticoid (GC) on bone formation and promotion of apoptosis of bone cells are thought to be the major mechanism of glucocorticoid-induced osteoporosis (GIO). GC reduces not only bone mineral density (BMD) but also bone quality, therefore, patients with GIO have a higher risk of fracture than those with postmenopausal osteoporosis with the same level of BMD. Recently, GC has been shown to suppress a Wnt signal pathway which is essential for bone growth.

Dehydroepiandrosterone-sulfate (DHEA-S), the sulfated form of dehydroepiandrosterone, is the most abundant steroids in human, although its biological activities are seemingly weak. Recently, basic and clinical observations suggest dehydroepiandrosterone (DHEA) increase bone mineral densities in the elderly. Large-scale double-blinded clinical trials are necessary.

Circulating plasma testosterone decreases by 0.5-1% per year after 40 age in men. Bone mineral density (BMD) in men also decreases by about 1% per year after age 40-60. Due to progression of an aging society, the frequency of osteoporosis in elderly men is gradually increased. Androgens have a major role in the growth and the maintenance of both cancellous and cortical bone mass in men. Androgen receptor is expressed in osteoblasts, osteoclasts and bone marrow stromal cells. Androgens have been shown to control the bone formation and resorption by regulating the expression and the activity of several cytokines and growth factors through androgen receptor. In addition to these direct actions, through the aromatase activity estrogens converted from androgens are converted to estrogens which act on bone tissues through estrogen receptor and play an important role in the homeostasis of cancellous and cortical bones in men.

Androgens have a major role in the growth and the maintenance of both cancellous and cortical bone mass in men. Androgen receptor is expressed in osteoblasts, osteoclasts and bone marrow stromal cells. Androgens have been shown to regulate the expression and the activity of several cytokines and growth factors, and control the homeostasis in bones. Dehydroepiandrosterone (DHEA) has a protective effect against osteoporosis in women after menopause through the intracrine mechanism in osteoblasts, which DHEA is converted to estrogen through the aromatase activity.

Glucocorticoid-induced osteoporosis(GIO)is the major cause of secondary osteoporosis, and prevention of GIO is thought to be essential to avoid bone fracture. Direct inhibitory effect of glucocorticoid on bone formation is considered as the main mechanism of GIO. Clinical guidelines have recommended that bisphosphonate is the first choice for the treatment of GIO. Bone mineral density in patients with GIO has recently been reported to be increased by the treatment with parathyroid hormone(PTH)at a low dose and by intermittent administration.

A strong positive correlation of serum dehydroepiandrosterone sulfate (DHEA-S) and estrone (E1) with bone mineral density (BMD) in postmenopausal women but no correlation between serum estradiol (E2) and BMD in the same group suggest that circulating adrenal androgen may be converted to estrogen in peripheral tissues including osteoblast and may contribute to BMD maintenance. Actually, in cultured human osteoblast cells, DHEA can be converted to androstenedione and then androstenedione to estrone through the apparent aromatase activity. In human bone cells, intracrine mechanism through aromatase activity may contribute to the local production of estrogens, thus leading to protective effect against osteoporosis especially after menopause.

Bone morphogenetic proteins (BMP) are cytokines that promote differentiation of mesenchymal stem cells into differentiated osteoblasts and bone formation. Recently, HMG-CoA reductase inhibitors (statins) emerged as a candidate for the treatment of osteoporosis, because they stimulate BMP-2 expression and bone formation. Inhibition of Rho/Rho-kinase pathway may be involved in statin effect on bone formation.