By Age 70 Men Lose Bone Mass at the Same Rate as Women

Valerie Serre, PharmD, PhD

Aging of the population is associated with the rising incidence of age-related conditions such as osteoporosis. In the US, as many as 41 million people could develop osteoporosis by 2015. Osteoporosis is a progressive microarchitectural deterioration of bone tissue, which induces skeletal fragility predisposing bone to fracture. This disease is mostly known to affect postmenopausal women. Osteoporosis in men has sparked interest because of the worrisome finding that 20% of people with osteoporosis are men. Men reach peak bone mass in their late 20s. The decline in bone mass becomes apparent in men in their 40s and by the age of 70 both men and women display an identical rate of bone loss. If left untreated, osteoporosis brings about complications such as pain, decreased quality of life, dependence, and fractures. These fractures are located mainly at the hip, vertebral wedge and wrist and are often associated with mortality. The dollar cost of this silent epidemic is enormous (over 10 billion US dollars per year in the United States), and it is likely to increase exponentially in the near future.

A Fragile Future for Men

Philip Dopp, BSc

The disturbing statistics with regard to the prevalence of osteoporosis among older women are well known. By 65 years of age, one in four women have experienced an osteoporotic fracture, and the rate of incidence rises to one in two by the age of 75. The incidence of hip fractures among women in the United States is 2 per 1000 patient years by the age of 65 and 30 per 1000 patient years by the age of 85.1 More importantly, hip fractures in the elderly are associated with a high mortality rate. Both men and women are between two and five times more likely to die during the first 12 months following a hip fracture when compared to age and sex matched controls without hip fractures. Given this and other serious consequences, there is much interest in discovering factors that can prevent or slow the rate of development of this disease.¹

Pathophysiology of Osteoporosis
Osteoporosis is the generalized, progressive diminution in bone tissue mass per unit volume which causes skeletal weakness, even though the remaining bone is normal morphologically. It is well known that factors that decrease bone mineral density (BMD) and increase the risk of osteoporotic fractures include family history, white race, female gender, estrogen deficiency, low dietary levels of calcium and vitamin D, limited physical activity or immobility and medications such as corticosteroids.^1,2 Currently, there has been an increased interest in determining the role that genetic factors play in the pathogenesis of osteoporosis.

Anna Liachenko, BSc, MSc

Canadian postmenopausal women now have a new drug option for treatment of established osteoporosis and/or relief of pain associated with osteoporotic fractures--synthetic salmon calcitonin administered as a nasal spray (Miacalcin Nasal Spray or Miacalcin NS). Already available in over 70 countries, the drug was approved in Canada in September of 1999. The nasal spray is very safe and has been shown in various studies to increase bone mineral density (BMD) in vertebrae, the primary site of fractures in postmenopausal osteoporosis. Several months ago a large clinical trial confirmed that Miacalcin NS lowers the risk of vertebral fractures, making it an important agent for osteoporotic therapy.⁶

Calcitonin is a peptide hormone secreted by the thyroid gland and its secretion is under the direct control of blood calcium levels. In humans, no definite effects on calcium levels are seen in states of calcitonin deficiency or excess. Calcitonin was discovered over 35 years ago by Dr. Harold Copp at the University of British Columbia. Secretion calcitonin is estrogen-dependent and is decreased after menopause.^7,8 Osteoporotics have lower levels of serum calcitonin than both premenopausal and healthy menopausal females. It is likely that the deficiency in the hormone plays some role in postmenopausal bone loss, and studies have found that calcitonin counteracts both early and established osteoporosis.

In one of the largest late-stage clinical programs ever conducted, the investigational pyridinyl bisphosphonate drug risedronate (Actonel) reduced the incidence of new vertebral fractures by up to 49 percent, and lowered the risk of osteoporosis related non-vertebral fractures by up to 39 percent. The results were presented at the annual meeting of the Endocrine Society.

Professor Richard Eastell, professor of bone metabolism at the University of Sheffield, UK, presented safety data from five clinical studies that enrolled a total of 5,226 post-menopausal women. The proportion of women reporting GI side effects was similar in the risedronate and placebo groups. Currently, risedronate is not available in Canada. For the full article see Nature 1999;397:315-23.

After twenty years of searching, Toronto researchers have located a gene in mice called opgl, that can activate mature osteoclasts and mediate osteoclastogenesis. The tumour-necrosis-factor family molecule osteoprotegerin ligand (OPGL), is an important factor for osteoclast maturation in vivo. Mice who lack the opgl gene exhibited severe osteopetrosis, stunted growth, defective tooth eruption and a complete lack of lymph nodes. Scientists also discovered that the gene was necessary for T- and B-cell maturation. Interestingly researchers found that OPGL secreted from activated T cells may "directly modulate osteoclastogenesis and the activity of mature osteoclasts." Although the implications of this discovery for humans are as yet undetermined, this may bring scientists one step closer to finding a cure for osteoporosis and T-cell-mediated arthritis.

For the full article see Nature 1999;397:315-23.

A 12 month, double-blind, placebo-controlled, randomized, multicentre study by Jencen and colleagues demonstrated that 5 mg/day of risedronate (Actonel) given for twelve months was effective in significantly increasing bone mineral density and lowering the risk of vertebral fractures, for patients on chronic corticosteroid therapy. From the abstract it is unclear if these fractures were clinically symptomatic, radiologically detected, or both. Risedronate prevents bone loss by inhibiting bone resorption. It represents a new type of biphosphonate which is hoped to have less gastrointestinal complications than other bisphosphonates, however, residronate is not available in Canada at this time.

Adachi and colleagues pooled results from two similarly designed, randomized, double-blind, placebo controlled trials examining the effectiveness of Etidronate (Didrocal) (which is available in Canada). Intermittent cyclical therapy with etidronate in patients recently starting corticosteroids proved to be effective in preventing bone loss in men, pre- and post-menopausal women. This data supports previously published studies employing a bisphosphonate to decrease the loss of bone mineral density with chronic systemic corticosteroid use.

Abstracts are available at http://ex2.excerptamedica.com/98ac

Shari Tyson, BSc, MSc

Contrary to popular belief, osteoporosis (OP) is not just an aging woman's ailment. About 8% of men can also expect to develop this disease. In fact, hip fractures in elderly men account for approximately one third of all hip fractures sustained due to OP. In addition, one third of those who have suffered such a fracture will not survive beyond a year. Yet despite the large numbers of men affected, and the millions of health care dollars allocated to the care of individuals with this disease, osteoporosis in men remains under-diagnosed, infrequently reported, and inadequately studied.

OP affects women to a greater extent than men. However, for several key reasons, men develop this disease at a much later age than women. For the first thirty years of life, the rate of bone formation exceeds the rate of resorption resulting in general bone growth and thickening. After peaking at age 30 for both sexes, the opposite is true; there is an increased rate of bone resorption and a general loss of bone mass. This rate is further accelerated in women when a dramatic decrease in estrogen production occurs at menopause.

Both estrogen and testosterone have been shown to play key roles in preventing the resorption process. The exact manner in which testosterone performs this function has yet to be discerned.