Men are not as resistant to osteoporosis as they may once have thought, and the classical age-related increase in fractures seen in women is also evident in men. One of the main reasons why osteoporosis is not as common in males as in women is the larger skeleton of the men. Other factors include the shorter life expectancy, later onset and slower progress of bone loss in men, and the absence of rapid bone loss that affects women as a result of menopause.

However, as understanding of the pathophysiology of the disease has increased in recent years, it's been recognized that the heterogenity of male osteoporosis represents an important public health issue, because of more precise tools to diagnose the disease through bone mineral density (BMD) measurements and more effective therapeutic approaches. Almost 30-40% of patients develop so-called "idiopathic" osteoporosis at a young age, in the absence of any detectable cause, whereas others have multiple evident reasons for bone loss, including glucocorticoid excess, hypogonadism, alcohol abuse, smoking, renal tubular disease with calcium wasting, or other liver or bowel disease.

Epidemiology of fractures

From adolescence through middle life, the overall fracture incidence is higher in males than females, most likely because of a greater incidence of traumatic fractures. After the age of 50 there is a reversal of this trend, as fragility fractures become much more common in women. However the incidence of these fractures increases rapidly with aging in men and the lifetime risks of low-trauma hip, clinical vertebral or radius fracture are estimated to be as high as 13% in a 50-year-old man and 25% in a 60-year-old man.

The incidence of hip fracture, the most serious fracture, increases exponentially in men as they age, as it does in women, but the age at which the increase begins is 5-10 years later than in women. It is estimated that approximately 30% of hip fractures worldwide occur in men. The consequences are worse than in women, and the incidence of this and other fractures is expected to increase markedly over the next several decades. The mortality rate during the first post-fracture month has been estimated at 10-14% in men, as compared to 5% in women. Previously considered uncommon in men, the prevalence of radiographic vertebral deformities was found similar in men and women aged 65 years or older and was higher in men under 65.

Back pain in the context of musculoskeletal diseases often reveals compression fractures that are sometimes difficult to distinguish from vertebral epiphysitis (Scheuermann`s disease) or other developmental changes. Men with vertebral fractures have lower vertebral and femoral BMD than do controls.

Determinants of fracture risk

As in females, body weight, nutritional status and other existing diseases are associated with increased fracture risk in males. The cause of the lower fracture rate in men is complex and associated with the accumulation of greater peak bone mass, less bone loss with aging, and fewer falls than in women.

Etiologies of osteoporosis in men

Osteoporosis in men is a heterogeneous condition with a wide variety of etiologies:

• Osteoporosis secondary to other disorders

Glucocorticoid excess is the most prominent of the secondary causes identified, accounting for 16-18% of the men evaluated. Steroids inhibit osteoblastic collagen synthesis but also reduce testosterone levels.

Hypogonadismis a well-established cause of osteoporosis in men and of failure to achieve peak bone mass in case of pubertal hypogonadism. Androgens are essential for the maintenance of bone mass in adult men and all forms of hypogonadism are associated with reduced BMD and fractures (castration, treatment with GnRH agonists, hyperprolactinemia, anorexia, hemachromatosis). Estrogens, particularly estradiol, have recently been implicated in the pathogenesis of male osteoporosis because a part of the testosterone produced in males is converted to estradiol under the influence of the enzyme aromatase. Cases of patients with an aromatase gene mutation and osteoporosis despite normal serum androgen levels have been reported.

• Main causes of osteoporosis in men

Primary:
- Idiopathic osteoporosis
- Aging

Secondary:
- Glucorticoid excess
- Hypogonadism
- Gastrointestinal disorders
- Alcoholism
- Hypercalciuria
- Immobilization
- Smoking

Alcoholism: Although there is a definite relationship between alcohol abuse and bone loss, the mechanisms by which alcohol induces bone disease remain unclear. They include an increased incidence of trauma, a reduction of osteoblastic activity, nutritional deficiencies and hypogonadism.

Smoking:Tobacco is linked to an increased prevalence of vertebral fractures in men, most likely due to vascular problems, relative immobility and comorbidity.

Hypercalciuria and renal stone disease:Several reports have linked hypercalciuria or nephrolithiasis in men to a reduction in BMD. A variety of other conditions have been associated with bone loss or fractures in men including gastrointestinal disorders, immobilization, thyrotoxicosis, liver disease, anticonvulsive use etc. Osteoporosis in men is termed "idiopathic" if no known cause can be identified on clinical and laboratory grounds. This is observed in about one third of men seen for evaluation of fractures, and in this population a family history of fracture is not uncommon.

Diagnosis and identifying men at risk

The presence of a vertebral fracture or deformity on X-ray should raise the probability of osteoporosis and lead to a bone density measurement. As in women, there is in men an inverse relationship of bone mass to fracture, the degree to which low spine or hip BMD increases fracture risk appearing to be similar in men and in women. Most hip and vertebral fractures in men are probably the result of low bone density or osteoporosis. In this context direct measurement of BMD is necessary to accurately diagnose osteoporosis and low bone mass. However, standardized published criteria for defining at-risk groups of men do not exist at present, because data regarding the relationship between BMD and fracture risk in men are limited and because men have larger bones and therefore a different geometry. In women, the threshold of 2.5 standard deviations (SD) below young adult normal BMD for the diagnosis of osteoporosis, according to WHO criteria, is an empiric choice based on the lifetime risk of fracture relative to the distribution of BMD measurements.

Routine laboratory testing should include sedimentation rate, serum calcium, phosphate, creatinine, total and/or bone alkaline phosphatase, serum cross-laps (bone-derived degradation products), 25-hydroxyvitamin D3 (25 OHD), parathormone, free testosterone, luteinising hormone (LH), and 24-h urine calcium, creatinine, urinary cross-laps or other collagen telopeptide. A biochemical profile including low serum calcium, low 25 OHD and high serum parathormone will suggest a differential diagnosis of osteomalacia, which could be confirmed by a hisomorphometric analysis of a transiliac bone biopsy.

Prevention and treatment

The principles of fracture prevention in men are similar to those in women: modifiable risk factors, including smoking inadequate calcium and/or vitamin D, excessive alcohol intake and inadequate exercise should be addressed. Current guidelines recommend 1200 mg of calcium per day, with suggested vitamin D intakes of 400-600 IU after the age of 50.

Regarding treatment, there have been only a few trials of osteotropic therapies performed specifically in men. In the first large controlled trial of a bisphosphonate over 2 years in men with osteoporosis, alendronate increased BMD significantly at all sites independently of serum testosterone and estradiol levels. More importantly, there was also a significant decrease in vertebral fractures. Positive effects of alendronate and risedronate on BMD and vertebral fracture rate were also found in males with glucocorticoid-induced osteoporosis.

Parathyroid hormone, which has been shown to exert striking increases in BMD and decreases in fracture incidence in postmenopausal osteoporotic women, seems to have also a great potential for male osteoporosis.

Thiazide diuretics have a hypocalciuric effect in osteoporotic men with hypercalciuria. Fluoride may have some benefit in men. Testosterone replacement increases bone mass in hypogonadal men, but the use of androgen therapy in eugonadal or aging men has an uncertain benefit because of its potential adverse effects on the prostate. Furthermore there are no prospective studies on fracture prevention.