3 Supplementation For Primary Prevention of Fractures
A Review of the Literature

Ryan Foster, MD, Department of Medicine, University of Toronto, Toronto, ON.

Matthew T. Oughton, MD, Department of Medicine, McGill University, Montreal, PQ.

Shabbir M.H. Alibhai, MD, MSc, FRCP(C), Staff Physician, Department of Medicine, University Health Network, Toronto, ON.

Fractures are a significant cause of morbidity and mortality in older adults. Previous studies indicated that fracture prevention with vitamin D supplementation, with or without calcium, was achievable only in limited populations. The most recent trial in this field, a randomized, placebo-controlled study by Trivedi, et al., found that large vitamin D doses given every four months are effective for primary prevention of fractures in the community-based older population. This study is critically reviewed in the context of previous studies, and recommendations are made about the role of calcium and vitamin D supplementation in fracture prevention.
Key words: osteoporosis, fracture prevention, vitamin D, calcium, supplementation.

Karen Beattie, BSc, PhD Candidate and Dr. A. Papaioannou, MSc, MD, FRCP(C), Associate Professor of Medicine; Department of Geriatrics, McMaster University, Hamilton, ON.
Dr. P. Boulos, MD, FRCP(C) and Dr. J.D. Adachi, MD, FRCP(C), Professors of Medicine; Department of Rheumatology, McMaster University, Hamilton, ON.

Osteoporosis is a major health concern in Canada, affecting 25% of women and 12% of men. Vertebral compression fractures, the most common of all osteoporotic fractures, are clinically diagnosed only 30% of the time. Treatment for such fractures is primarily pharmacological. However, newer, non-invasive methods of treatment, namely vertebroplasty and kyphoplasty, stabilize compression fractures, provide pain relief and even improve posture and functional ability. While vertebroplasty involves the injection of a cement product into one or more compressed vertebrae, kyphoplasty adds another step of inserting a balloon into the vertebra to re-establish original vertebral height. Clinical studies of these procedures suggest kyphoplasty provides better symptomatic relief and is associated with fewer complications than vertebroplasty. However, further randomized, controlled evidence comparing these procedures is required.
Key words: kyphoplasty, vertebroplasty, osteoporosis, vertebral fracture, compression fracture.

Bisphosponates are the only medications currently available that have been demonstrated in large randomized trials to reduce the risk of hip fracture. Unfortunately, bisphosphonates have low oral bioavailability and can cause esophageal inflammation or ulceration, restricting maximal dosage. These characteristics necessitate frequent administration on an empty stomach, which may limit patient compliance.

Thus, it was with great excitement that researchers released the results of a one-year, randomized, double-blind, placebo-controlled trial on five different regimens of zoledronic acid, a potent bisphosphonate. Participants received placebo or intravenous zoledronate in doses of 0.25 mg, 0.5 mg or 1 mg, at three-month intervals. In addition, one group received a total annual dose of 4 mg as a single dose, and another received two doses of 2 mg each, six months apart. The primary endpoint of the study was lumbar-spine bone mineral density.

Interestingly, all five drug treatment schedules had about the same results, and all were better than placebo. Bone mineral density in the spine was 4.3 to 5.1% higher in all treatment groups than in the placebo group (p<0.001) and values for the femoral neck were 3.1 to 3.5% higher than placebo (p<0.001). In addition, biochemical markers of bone resorption were significantly suppressed throughout the study in all zoledronic acid groups, despite the fact that by 24 hours after administration, drug levels were less than 1% of the post-administration peak and 40% of the dose has been excreted in the urine.

The drug was generally well tolerated, and rate of retention of subjects was high. However, studies that demonstrate an effect on the rate of fractures are needed before any recommendations can be made.

Over a million people in Canada are affected by Osteoporosis, a syndrome that leaves them at higher risk of fracture, disability and even premature death.

Source

1. Reid IR, Brown JP, Burckhardt P et al. Intravenous zoledronic acid in postmenopausal women with low bone mineral density. NEJM. 2002;346:653-61.

Chui Kin Yuen, MD, FRCSC, FACOG, FSOGC, MBA, Chairman, Manitoba Clinic, Winnipeg, MB.

Current History
Mrs. Brittle Bone presents to your office because of low back pain of insidious onset in the past three weeks. Mrs. Brittle is a healthy 68 year old female and is an active gardener. Following the death of her husband one year ago, she continued to live in her house and has done many of the household chores, including gardening. Her pain began three weeks ago and, since then, she has found it difficult to do her household work. She is not able to rest peacefully at night because of the discomfort.

Family History
She has no family history of osteoporosis. However, her mother was diagnosed with breast cancer at 55 years old.

Lifestyle Habits & Medications
Mrs. Brittle Bone is a healthy non-smoker with adequate nutrition and regular exercise. She drinks occasionally. She takes calcium and vitamin D supplements every day. She is not on any medications and has never been on Hormone Replacement Therapy.

Physical Examination
Physical examination of the spine demonstrates that she has mild kyphosis. Her range of motion is limited and the pain is exacerbated with extension and rotation. Percussion of the spine reveals point tenderness at L2.

Dr. Gabriel Chan, MBBS(HK), FHKAM, MRCP(UK), ABIM, FRCP(C), FRCP(EDIN),
Director of Geriatric Medical Services and Program Medical Director of Long-Term Care, North York General Hospital, Lecturer of Medicine, University of Toronto, Toronto, ON.

Frances Simone, BSc, MHA, Director, Geriatric Ambulatory Care Services, North York General Hospital, Toronto, ON.

The POWER (Promoting Osteoporosis Wellness through Education, Exercise and Resources) program is a collaborative, multi-site initiative designed to empower older adults with osteoporosis to improve their quality of life and prevent falls. POWER consists of a seven-week, culturally sensitive education, exercise and nutrition program developed by North York General Hospital, Baycrest Centre for Geriatric Care, Toronto Public Health and Yee Hong Centre for Geriatric Care. POWER is an effective health promotion model for osteoporosis management and falls prevention that can be replicated in other communities across the country.

Health promotion and disease prevention are very important concepts that support our collective goal for a healthy society. Currently, there is a need to develop models that fully integrate health promotion activities into our 'illness treatment' oriented health system. Without such models, we will face significant challenges as our population ages and our health system attempts to cope with the impact of chronic diseases.

D'Arcy Little, MD, CCFP, Director of Medical Education, York Community Services, Toronto and Academic Fellow, Department of Family and Community Medicine, University of Toronto, Toronto, ON.

Introduction/Epidemiology
Osteoporosis is a common, serious disease in older adults. Until recently, osteoporosis research and treatment have focussed on postmenopausal women. Recently, however, the epidemiology of this condition in elderly men has become clearer and it is evident that osteoporosis is also prevalent in this population. In fact, men over the age of 50 years have a 19-25% lifetime risk of an osteoporotic fracture, as compared to women who have a 50% lifetime risk. In addition, it is estimated that 30% of hip fractures that occur worldwide occur in men, and lead to significant mortality and loss of independence. Indeed, post-hip fracture, men have a higher mortality rate than do women.^1,2,3,4 The role of androgens in bone physiology has suggested that testosterone may be one arm in the treatment regimen. The following article will review the place of testosterone in the management of osteoporosis in males.

Bone Physiology and Pathophysiology
Osteoporosis is a "disease characterized by low bone mass and microarchitectural deterioration of bone tissue leading to enhanced bone fragility and a consequent increase in fracture incidence."⁵ The origin of idiopathic osteoporosis lies in the aging process and normal bone physiology.

Jan Bruder, MD, Assistant Professor and Director of Osteoporosis Metabolic Bone Clinic, Division of Endocrinology, University of Texas Health Science Center, Department of Medicine, San Antonio, TX, USA.

Introduction
Osteoporosis is a disease characterized by low bone mass and bone strength, resulting in an increase in bone fragility and susceptibility to fractures.¹ It is asymptomatic prior to fractures, which most commonly occur in the vertebral body, hip and forearm.

Dual energy x-ray absorptiometry is the technology used to measure bone mineral density at the sites of interest. This technology has revolutionized our approach to this disease. In 1994, the World Health Organization (WHO) published diagnostic guidelines for osteoporosis, which are based on an individual's bone mineral density (BMD) according to a T-score.² The T-score is defined as the number of standard deviations (SD) above or below the mean BMD at peak bone mass at age 30 years. A T-score of -2.5 or lower defines osteoporosis. At risk individuals can now be diagnosed early, thereby allowing the use of highly effective interventional strategies which prevent further bone loss and potentially debilitating fractures. Unfortunately, currently once significant bone mass has been lost, there are no commercially available therapies that are proven to increase bone density. This will likely change in the next few years.

Sophie Jamal, MD, FRCPC, Osteoporosis Research Fellow, Sunnybrook and Women's College Health Sciences Centre, Toronto, ON.

Osteoporosis, defined as a reduction in bone mass leading to an increased susceptibility to fracture with minimal trauma, affects 1.4 million Canadians.¹ Osteoporotic hip and vertebral fractures are major causes of disability and premature death. For example, the average length of stay in an acute care hospital after a hip fracture is three weeks, and one in four patients must remain in long-term care institutions for at least one year. Furthermore, patients with hip and vertebral fractures face a 20% increased risk of mortality.² Osteoporosis is also costly--in Canada, in 1993, the total expenditure for fractures was estimated to be 1.3 billion dollars.³ As the population of Canada ages, the impact of osteoporosis will increase. As such, health care providers should be aware of techniques to prevent fractures due to osteoporosis.

In addition to encouraging physical activity and ensuring adequate calcium and vitamin D intake, several medications can be used to prevent osteoporotic fractures. These drugs, which have been studied predominantly in postmenopausal women, include bisphosphonates, estrogen, selective estrogen receptor modulators and calcitonin. The evidence that supports the use of these agents to prevent bone loss and fractures in postmenopausal women is reviewed below.

There is no doubt that osteoporosis is yet another syndrome that can be characterized as 'silent.' The long period of bone loss is characteristically asymptomatic until the first clinical fracture occurs. However, even when the diagnosis is being shouted aloud (via a fracture requiring hospitalization), only a small minority of patients actually has the diagnosis of osteoporosis recorded on the hospital chart. Furthermore, it is likely that an even smaller proportion receives effective treatment, sometimes despite hospitalization for an osteoporotic fracture. Surveys of apparently healthy women in primary care practices reveal a prevalence of osteopenia and osteoporosis that approaches 50%; yet most of these women are not diagnosed as having bone disease.

What are the reasons for this? Clearly, the lack of symptoms prior to the first fracture is very important. In other disorders, the best example being hypertension, the medical community and the public at large understand the importance of diagnosis before the first clinical disaster occurs. In addition, screening for that disorder (by using a blood pressure cuff) is relatively easy and inexpensive. Hopefully, new techniques for determining bone density (particularly ultrasound) will be cost effective for primary care in the future. Another contributing factor may be that, until recently, there was a paucity of proven effective treatments for osteoporosis. We now have several excellent medications, with the prospect of more to come in the near future.

One cannot help but wonder if the fact that osteoporosis is a 'woman's disease' has also contributed to its relative neglect in the past. Certainly, many of the best young clinicians and investigators in the field are now women, and this should keep the focus on the problem of 'bone health' in the future. It is also interesting to note that the problem of male osteoporosis is finally coming to light. It is surprising that we have been blind to this fact for so long, considering that up to one quarter of hip fractures occur in elderly men.

This edition of G&A has several articles on the topic of osteoporosis. We can learn about the standard pharmacological management of osteoporosis in Sophie Jamal's article, while Jan Bruder's piece outlines new possibilities for the prevention and treatment of osteoporosis. I am particularly pleased that D'Arcy Little has written about osteoporosis in men (possibly my male bias showing). Frances Simone and Gabriel Chan tackle one of my favourite topics, the interface between osteoporosis and the classic geriatric syndrome of falls. Simone and Chan present a new type of program designed to tackle both sides of the fracture problem: bone density and the propensity for falls. We also have the first of our case studies series, which discusses the management of osteoporosis in an elderly woman (Chui Kin Yuen).

In addition, we have our usual collection of geriatric articles. Ann-Sophie Rigaud and Bernard Forette discuss the treatment of hypertension; despite the fact that it is now over 15 years since the first randomized trial on the efficacy of treatment of hypertension in the elderly was published, we do a very poor job of diagnosing and effectively treating hypertension in the elderly. There is an article on aphasia by Farcnik, Persyko and Bassel, and one by Ozdal and Tanguay on a new treatment for benign prostatic hyperplasia. Miller and Lemmons discuss the ethical (and legal) issues when clinicians are paid finder's fees for finding subjects for research studies. Jerilynn Prior reviews estrogen and progesterone therapy in older menopausal women and Kathryn Yorkston and her colleagues give advice on managing dysarthria in patients with ALS.

Enjoy this issue.

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