US Pharm. 3013;38(9):HS-20-HS-24.

Osteoporosis (bone thinning) makes the bones porous and is the main cause of fractures. Two million American men already have osteoporosis, and 12 million are at risk of bone loss and low bone density. Nevertheless, men are still at lower risk of bone loss compared to women. The vertebrae are often the first bones affected, causing a loss of half an inch or more in height. In later ages, if there is a loss of height, the first-step analysis is to measure the bone density.1

OVERVIEW

Most of the time, osteoporosis is detected by an x-ray taken for a fracture or other condition. The rate of osteoporosis is four times higher in women than in men due to menopause and a longer life span. Because men are generally more physically active over the course of their lives, they lose less bone mass, as physical activity has proven to increase bone density.1

In general, osteoporosis in men is considered a symptom of testosterone deficiency, whereas in older women it is almost always a postmenopausal outcome. When men are evaluated for osteoporosis, their testosterone levels are also measured.2

Although men with low testosterone are recommended for testosterone replacement to build bone mass, the science has not yet shown to what extent the bone-building benefit is a direct testosterone effect or the result of turning testosterone into estrogen. It is important, therefore, not to minimize the role of testosterone-to-estrogen conversion. Estrogen preserves bone density in both men and women. Men normally convert testosterone to estrogen in a slow rate to build bone mass.2

Men who genetically lack an enzyme to make even small amounts of estrogen are prone to osteoporosis; this is shown by the fact that if they receive estrogen, their osteoporosis improves. So even though estrogen is not present in very high concentrations in the blood of men, it is a critical factor for bone health.2

BONE REMODELING

Over a course of 10 years, the human skeleton is completely replaced with new bones at a rate of 10% per year. In this natural process, called bone remodeling, old bone cells are replaced with new bone cells.2

This is a continuous process of bone resorption and bone formation for the purpose of maintaining normal bone mass. Normal bone mass indicates healthy bones that are strong and free from osteoporosis. There are three sets of cells involved in this process: osteoclasts, which are responsible for bone resorption (breakdown); osteoblasts, which are vital in the formation of bones; and osteocytes, which send the signals that bones are being exposed to stress or injury.2

Strong bones give structural support to the whole body and are important storage sites of calcium. With bone remodeling, the body is also able to repair small bone fractures that occur from daily physical activities.3

The bone-remodeling cycle usually starts when injury or mechanical stresses occur in bones. Calcium, magnesium, and vitamin D are necessary elements in the construction of solid bone mass.3

CAUSES OF MALE OSTEOPOROSIS

Exercise and mechanical stress have a major impact on bones, and without exercise both bone and muscles are weakened. It is reported that only about 35% of men aged 25 to 64 years meet the minimum daily exercise prescription of 30 minutes of brisk walking on most days of the week. Studies have shown that exercise boosts bone mass at the sites of skeletal stress. As an example, walking or jogging can only increase bone density in the hips.3

Medications

The following groups of drugs can impact the bones both in men and women.

Corticosteroids: The physiology of corticosteroid-induced osteoporosis in men is different from that of postmenopausal osteoporosis in women, so treatment cannot be expected to have the same results. The anti-inflammatory steroids that depress the body’s immune response—such as cortisone, glucocorticoids, and prednisone—weaken bone density. Corticosteroids that treat a variety of disorders can interact with bones. There is a dose-dependent effect, which is difficult to define because of varying durations at each dose. In one study, doses of prednisone > 7.5 mg/day for a year shut down new bone growth completely and speeded up the normal loss of old bone.3

The beneficial effects of steroids in patients with comorbid disease may partially offset the detrimental effects on bone, yet these steroids cause osteoporosis and fractures in a high percentage of patients. Because the effects are so variable and can be clinically severe, patients going on long-term steroid treatment should have their bone density monitored and measures should be taken to try to preserve bone. The trabecular bone is affected more rapidly than the cortical bone. Some patients suffer multiple vertebral fractures within a year of initiating steroid therapy. The mechanism of bone loss by corticosteroids is summarized as follows: inhibition of osteoblast function; enhancement of bone resorption; inhibition of gastrointestinal calcium absorption; increased loss of urine calcium; and inhibition of gonadal hormones.3

To prevent and treat steroid-induced osteoporosis, adequate calcium intake (1,000-1,500 mg/day) is needed. This is enough in average men, since higher amounts may not have beneficial effects. The use of vitamin D in this kind of osteoporosis is not supported with enough literature; however, most clinicians recommend 1,000 IU/day to prevent the deficiency of this vitamin. In severe cases of vitamin D deficiency, more potent forms such as calcitriol at doses of 0.25 mcg/day must be used. Gonadal steroid in men and women should be replaced unless there are contraindications.4

Another approach to maintain bone density is the use of antiresorptive drugs, or bisphosphonates, such as alendronate, ibandronate, risedronate, and injectable zoledronic acid. These drugs slow or stop the natural process that dissolves bone tissue, resulting in maintained or increased bone density and strength. If osteoporosis has already developed, slowing the rate of bone thinning reduces the risk of broken bones. Calcitonin nasal spray (one puff = 200 IU/day) or bisphosphonates (alendronate 5 mg/day) have been used successfully. For patients who take these drugs, the magnitude of improvement is higher in postmenopausal than in steroid-induced osteoporosis. This is because the antiresorptive medications do not help with the osteoblasts, which are inhibited by the corticosteroids. The important fact is that these therapies should not be used in patients with low serum calcium, and adequate dietary intake should be established before they are started.5

Antiseizure Drugs: People with epilepsy have a higher risk than average of broken bones and fractures. One of the reasons for their lower bone density is that antiseizure drugs interfere with the absorption or metabolism of calcium and vitamin D, both considered natural bone supplements. So any person taking antiseizure drugs—whether male or female—should take at least 1,200 mg of calcium and at least 1,200 IU of vitamin D per day. This includes young children who are also highly vulnerable. In addition, patients should be informed that osteoporosis and osteomalacia are possible side effects of some antiepileptic drugs, and preventive measures should be taken. All men over age 65 years who have taken these drugs for a long period of time should have a bone density scan. Some of the risk factors for bone fracture are falls during sei zure attacks; taking antiseizure drugs such as carbamazepine, primidone, phenobarbital, phenytoin, topiramate, and sodium valproate; being a woman who has undergone menopause; and being an older male and rarely going out in the sunshine.6

The mechanism of action for adverse effects of antiseizure drugs, especially phenytoin, on bones is attributed to their CYP450-inducing effect. Not all of these drugs have the same effects, and their action varies. Chronic use may result in decreased vitamin D concentrations due to hepatic enzyme induction, and may lead to hypocalcemia and hypophosphatemia. The effect of calcium and exercise has not been assessed in people with epilepsy.

The Osteoporosis Knowledge Test (OKT) is a validated, 24-item test. This test is administered to measure knowledge of risk factors for osteoporosis and strategies for prevention related to calcium and exercise. In many cases, independent t tests of the individual OKT questions revealed specific knowledge deficiencies in the areas of risk factors, exercise, and reasons for calcium supplementation for non-Caucasians. Results of this study have revealed that people with epilepsy, who are at greater risk for metabolic bone loss, have lower knowledge scores for calcium and exercise than nonepilepsy populations of various ages and genders.7 Culturally relevant epilepsy materials and programs may improve knowledge and adoption of preventive behavior.7

Drugs for Prostate Cancer:   Hormone therapy with gonadotropin-releasing hormone (GnRH) agonists (i.e., flutamide, bicalutamide, and nilutamide), which are often used for men with advanced prostate cancer, can lead to low bone mineral density and a higher rate of fractures. Long-term use of these drugs causes osteoporosis and impacts quality of life in men.8

Medical Conditions

A long list of diseases can lead to low bone mass, from genetic conditions like cystic fibrosis to diabetes, rheumatoid arthritis, and digestive and blood disorders.9 Here, we mention a few more.

Low Magnesium–High Calcium Ratio: Calcium and magnesium are the major minerals in the body, and they need each other to work properly. The Western diet is low in magnesium and high in calcium, and this is due to a high intake of dairy products. The calcium-to-magnesium ratios found in milk, yogurt, and hard cheeses are 7:1, 11:1, and 26:1, respectively. The average calcium intake is about 1,000 mg/day.9

The calcitonin hormone that inhibits osteoclast production relies on magnesium to function properly. When magnesium levels are too low, more osteoclasts are produced than should be, and this causes low bone density and, eventually, osteoporosis.9

There is a difference between serum magnesium level (extracellular) and red blood cell (RBC) magnesium level (intracellular). Even if the magnesium is very low, the blood will almost always test normal because the body pulls magnesium from cells into the blood to maintain normal serum magnesium levels. Therefore, the intracellular magnesium levels (RBC) are the real indicator of actual magnesium levels in the body.9

Thus, the low magnesium intake with high calcium intake common to our Western diet is most likely one of the main reasons for osteoporosis in most people. Worldwide reports from Asian and African populations show that with a low intake (about 300 mg) of calcium daily and a higher magnesium intake, the occurrence of osteoporosis is very low.9

Gonadal Hormones Deficiency: In men, low testosterone levels are the issue. Decreased testosterone levels cause increased osteoclast activity, which results in bone loss. Because testosterone levels decrease with age, the older a man gets the more likely he is to develop osteoporosis.9

In women, osteoclast, or bone removal, activity increases after menopause because estrogen levels decrease. During the first 5 to 10 years after menopause, women can suffer up to 2% to 4% loss of bone density per year and up to 25% to 30% of their bone density during that time period.9

Low Thyroid Function: Osteoclasts are activated by the parathyroid hormone, which signals them to resorb bones. Calcitonin is the hormone that inhibits the activity of osteoclasts so that they do not resorb too much of a person’s bones. Calcitonin is primarily made by the thyroid gland. Thus, low or poor thyroid function interferes with calcitonin production, so the osteoclasts are not inhibited to the degree they need to be, resulting in too much bone resorption.9

Smoking and Nicotine Effect

Nicotine has a direct toxic effect on bone-making cells (osteoblasts). Smokers have a higher risk of fracture—a 55% higher risk of hip fracture than nonsmokers, as well as lower bone mineral density. Cigarette smoke generates large amounts of free radicals, molecules that attack the body’s natural defenses. The result is a chain reaction of damage throughout the body, including cells, organs, and hormones involved in keeping bones healthy.10

The toxins upset the balance of hormones (like estrogen) that bones need to stay strong. In women, smoking adds to the bone loss that is already occurring in the menopausal years. Smoking increases levels of the hormone cortisol, which leads to bone breakdown, and decreases the hormone calcitonin, which helps build bones.10

Smoking also damages blood vessels, so there is poor blood supply of oxygen. Studies show that a smoker who suffers a fracture heals poorly because of poor blood supply. Heavy smoking further increases the risk of fracture.10

Bone building is a slow process, and it takes a long time to fix the damage, so some of the damage may be irreversible. The more heavily a person smokes, the longer it will take to recover bone loss.10

Exercise for Strong Bones

Many men have spent a lifetime playing sports, especially during adolescence, so it may be easier for them to commit to exercise in their later years. This is very helpful in older age, when bone building has slowed.

Exercise can preserve bone mass, especially if it is the right kind. Weight-bearing exercise and impact sports are best for maintaining bone mass. Jogging, hiking, mountain biking, and jumping rope are high-impact activities. Walking, skiing, and inline skating are low impact. Ideally, the experts say to do at least 30 minutes of moderate activity, like brisk walking, on most days of the week and strength training, like weight lifting or resistance training with weight machines, twice a week.

Supplemental Calcium and Vitamin D

The same advice for calcium holds true for men as for women. If there is a sign of low bone mass, the medical experts’ recommendation is to take 1,000 mg of calcium a day from ages 19 to 50 years and 1,200 mg of calcium a day over age 50 years.11

In addition, enough vitamin D is needed to absorb calcium; otherwise, all that calcium goes to waste. The recommended daily allowance for adults is 400 IU of vitamin D. Some doctors suggest taking as much as 800 to 1,200 IU in people with osteoporosis. People with osteoporosis or osteopenia who live in a climate without much sun need even more, as sunlight is the body’s primary source of vitamin D.11

Conclusion  

It is important to monitor a possible hormone deficiency or medical condition that could be weakening the bones. Bone mass does matter, and healthy bone mass can prevent a hip fracture, which can be disastrous in later life due to its complications.

A realistic goal is to prevent fractures. Although reversing osteoporosis is not completely possible, reversing the consequences of osteoporosis may be.

REFERENCES

1. U.S. Preventive Services Task Force (2011). Screening for osteoporosis: recommendation statement. www.uspreventiveservicestaskforce.org/uspstf10/
osteoporosis/osteors.htm. Accessed June 1, 2012.
2. Lewiecki EM. In the clinic. Osteoporosis. Ann Intern Med. 2011;155(1):ITC1-1-15/16.
3. Beling PR. Clinical practice. Osteoporosis in men. N Engl J Med. 2008;358(14):1474-1482.
4. Khosla S. Increasing options for the treatment of osteoporosis. N Engl J Med. 2009;361(8):
818-820.
5. Qaseem A, Snow V, Shekelle P, et al. Pharmacologic treatment of low bone density or osteoporosis to prevent fractures: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2008;149(6):404-415.
6. Gross RA, Gidal BE, Pack, AM. Antiseizure drugs and reduced bone density. Neurology. 2004;62(11):E25-E25. www.neurology.org/
content/62/11/E24.full. Accessed June 15, 2012.
7. Yood RA, Mazor KM, Andrade SE, et al. Patient decision to initiate therapy for osteoporosis: the influence of knowledge and beliefs. J Gen Int Med. 2008;23(11):1815-1821.
8. National Institutes of Health. What prostate cancer survivors need to know about osteoporosis. www.niams.nih.gov/Health_Info/Bone/
Osteoporosis/Conditions_Behaviors/osteoporosis_prostate_cancer.asp. Accessed July 20, 2012.
9. Qaseem A, Snow V, Shekelle P, et al. Screening for osteoporosis in men: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2008;148(9):680-684.
10. Osteoporosis Health Center. www.webmd.com/osteoporosis/smoking-and-osteoporosis?
page=1. Accessed August 30, 2012.
11. Tang BM, Eslick GD, Nowson C, et al. Use of calcium or calcium in combination with vitamin D supplementation to prevent fractures and bone loss in people aged 50 years and older: a meta-analysis. Lancet. 2007;370(9588):657-666.

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