Male osteoporosis: A review, "Beyond the Abstract," by Antonio Herrera, MD, PhD, et al

BERKELEY, CA (UroToday.com) - Osteoporosis in men is a heterogeneous disease that has received little attention. However, one third of worldwide hip fractures occur in the male population. This problem is more prevalent in people over 70 years of age. Increased life expectancy in the USA and the Western world has resulted in a higher incidence of male osteoporosis in patients aged 70 to 85. Up to 34.7% of individuals in that interval fulfilled osteoporosis criteria and, in addition, 50% of men over the age of 50 had osteopenia.

Male osteoporosis can be classified into three groups: a) Involutional or senile osteoporosis, b) Idiopathic osteoporosis, and c) Secondary osteoporosis.

a) Involutional or Senile Osteoporosis
Although hormonal changes in men are not so marked as in females, they are also important in the pathogenesis of osteoporosis. Sex-hormone binding globulin (SHBG) levels increase with aging in men. On the contrary, serum bio-available (or non-SHBG bound) estradiol and testosterone levels decrease with age. Bone mineral density (BMD) is clearly related with steroid levels, especially with bio-available estradiol levels.

b) Idiopathic Osteoporosis is clearly related to genetic alterations, mainly gene polymorphisms

c) Secondary Osteoporosis
Secondary osteoporosis is associated with a number of etiologies, the most common of which are: hypogonadism, vitamin D deficiency and inadequate calcium intake, hormonal treatments for prostate cancer, use of toxic substances, and every disease or drug use which disturbs bone metabolism.

c.1: Hypogonadism
Up to 66% of the elderly had testosterone and estradiol hormonal levels lower than the standard. Low hormonal levels are associated with muscle atrophy, resulting in an impairment of defense mechanisms against falls. Moreover, low levels of estradiol can increase the risk of fractures. The drop in estradiol levels might be caused by a deficit of testosterone transformation into estradiol due to an aromatase enzyme dysfunction. There are several reports along these lines documenting severe male osteoporosis induced by mutations of the estrogen-receptor of the aromatase enzyme.

c.2: Vitamin D deficiency and inadequate calcium intake
Vitamin D stimulates intestinal calcium absorption and is essential for bone metabolism. Low levels of vitamin D in men over 65 years of age are very common. It has been considered that about 15% of male osteoporosis cases are related to this deficiency. An adequate daily calcium intake is essential for bone metabolism (1 200 mgs per day). If, as usual, it is also associated with low vitamin D serum levels, the negative consequences for the mineral metabolism and the health of the individuals are even greater.

c.3: Hormonal treatments for prostate cancer
Prostate cancer, a prevalent male disease, can be treated in some cases with androgenic suppression, which is a major risk factor for osteoporosis.

c.4: Toxic habits
Tobacco, alcohol and coffee have been associated with osteoporosis. Alcohol consumption is the most dangerous of them. Prevalence of regular drinkers in the male population is often significant. Heavy drinkers have major alterations in bone metabolism.

Other Causes

Secondary osteoporosis in men may also result from other medical conditions: anticonvulsant therapy, prolonged steroid therapies, rheumatoid arthritis or ankylosing spondylitis, primary hyperparathyroidism, hepatic and renal diseases, malabsorption syndromes, transplanted patients or those treated with immunomodulators, thyrotoxicosis, diabetes mellitus, hypercalciuria, and human immunodeficiency virus (HIV) carriers.

Diagnosis and Fracture Risk

The main difficulty is to establish the correct diagnosis in the absence of known causes of secondary osteoporosis or previous fragility fracture. Most of clinical guides recommend densitometry scanning for men over 70-years-old. After secondary osteoporosis diagnosis is made, we have to look at specific disorders affecting the bone.

The most important factors in assessing fracture risk are prior fragility fractures, bone mineral density (BMD) level, age and physical condition of the patient, and evaluation of drug therapies given to them for other pathologies. The FRAX scale, with or without BMD measurements, is a good tool for assessing osteoporotic fracture risk.

Treatment

Non-pharmacological Treatment

As a general rule, a healthy lifestyle, proper nutrition, the suppression of toxic substances, and an adequate intake of calcium (1 200 mgs / day) and vitamin D (800 IU / day) should be recommended. Physical exercise, particularly weight bearing activities, is also recommended.

Pharmacological Treatment

Unlike female osteoporosis treatment, which is supported by a number of clinical trials including thousands of patients with long term follow-up, male treatment raises concerns about the most appropriate drug therapy. Clinical trials on male osteoporosis treatment are focused on BMD improvement, while they have failed to demonstrate a reduction in the incidence of osteoporotic fractures, a problem which could be solved with long-term follow-up studies.

Bisphosphonates

Although there are not as many studies on the use of bisphosphonates in men as there are in women, some authors claim that their effectiveness is similar in both genders. However, evidence suggests a lesser reduction in fracture incidence in men than do in women. Alendronate, risedronate and ibandronate yield similar outcomes. Zolendronato (a single intravenous dose annually) is especially recommended for treating skeletal-related events in patients with prostate cancer and bone metastases.

Anabolic Drugs

Anabolic treatment with parathyroid hormone derivatives (teriparatide) increases spine and hip BMD and is recommended in men at high risk of fragility fracture. This anabolic therapy should not last for more than two years, then bisphosphonates can be used to continue treatment. Recently, combined bisphosphonates and teriparatide therapy has been suggested.

Testosterone Testosterone treatments are not usually recommended in the clinical practice guidelines. However, this hormone can markedly increase the quality and density of trabecular bone in young patients with hypogonadism, while increasing the lean muscle mass. But this hormonal therapy may produce severe side effects. In a recently published paper, no side effects have been reported in elderly with the use of low-dose (20mgs/day) of testosterone undecanoato.

Other Treatments

Denosumab, a monoclonal antibody that acts on the RANK-ligand, demonstrated an increase in BMD and a significant decrease in the incidence of vertebral fractures in patients undergoing androgen deprivation therapy. Selective estrogen receptor modulators (SERM), raloxifene and toremifene, had also been recommended in those patients, but thromboembolic side effects make its use not advisable in the elderly. Studies on the effectiveness of strontium ranelate in male osteoporosis have been recently published, although this drug is only approved for use in Europe.

Written by:
Antonio Herrera,a Jesus Mateo,a Antonio Lobo-Escolar,a , Jorge Gil,a Elena Ibarz,b and Luis Graciab as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.

a Department of Orthopaedic and Trauma Surgery, Miguel Servet University Hospital, Department of Surgery, University of Zaragoza, Spain
b Department of Mechanical Engineering, University of Zaragoza, Spain

Male osteoporosis: A review - Abstract

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