Workshop: Osteoporosis

Suneil Kapur, MD, BSc, Stephanie Myckatyn, MD, BSc

Osteoporosis is "a systemic skeletal disease of low bone mass and microarchitectural deterioration", with major social, medical and economic health implications worldwide. It is important for physicians to identify risk factors and prevent fractures, determine thresholds for treating disease and be aware of new anabolic agents for osteoporosis.

The National Osteoporosis Foundation (NOF) risk factors for osteoporosis include non-modifiable risk factors such as:
 • Advanced age
 • History of fracture in a first-degree relative
 • Caucasian race
 • Personal history of fracture as an adult
 • Dementia
 • Female sex
 • Poor health/fragility.

Modifiable risk factors include:
 • Weight less than 127 lbs
 • Cigarette smoking
 • Menopause less than age 45
 • Estrogen deficiency
 • Premenopausal amenorrhea > 1 year
 • Low life-long calcium intake
 • Impaired eyesight
 • Recurrent falls
 • Poor health/frailty
 • Inadequate physical activity.
 
All patients who are considered at risk for fractures should be on calcium and vitamin D.

The current NOF guidelines recommend initiation of treatment with bisphosphonates, calcitonin or selective estrogen receptor modulators (SERMS) at a T-score < -2.0, with no risk factors or use of age. However, the five-year risk of hip fracture, without treatment, in a 55 versus 80-year-old woman with these characteristics, is 0.5% and 5% respectively. This raises questions regarding the cost-effectiveness of the NOF recommendations.

The Fracture Index is a useful tool for estimating fracture risk. It is based on data from the Study of Osteoporotic Fractures, involving 7,782 women with dexascan of the hip and spine, followed over five years. Point values were assigned to risk factors such as:
 • Age
 • Previous fractures
 • History of fracture in mother
 • Weight less than 125 pounds
 • Smoking
 • Arm use to get out of chair
 • Bone mineral density (BMD).

There was a strong relationship between the Fracture Index and hip fracture risk.
 
Another model by Ettinger et al. estimated spine and hip fracture risk, using risk factors including:
 • Body mass index < 21
 • Age
 • Smoking
 • Sister or mother with hip fracture
 • Previous spine or non-spine fractures
 • Hip and spine Z-scores.

A computer program was generated to estimate the five-year fracture risk, risk after treatment, number needed to treat and cost-effectiveness.

Estrogen replacement therapy has been shown to reduce the risk of vertebral and non-vertebral fractures in case-controlled and cohort epidemiological studies. However, the extra-skeletal effects are still controversial. A large, placebo-controlled study of postmenopausal osteoporotic woman, taking 200 IU of intranasal calcitonin over five years, showed a 33% reduction (p<0.03) in new vertebral fractures.

Amongst the bisphosphonates, in a large randomized controlled trial, etidronate significantly decreased the relative risk of spine fractures after two years. Similarly, alendronate and residronate have been shown to reduce the risk of vertebral fractures by 45 to 50%, compared to placebo over three years. In addition, alendronate and residronate reduced the risk of non-vertebral fractures by about 40 to 50%, compared to placebo.

In a recent randomized, placebo-controlled trial of 7,700 osteoporotic women, raloxifene, a SERM, was found to reduce the risk for vertebral fracture by 50% in those with no prior vertebral fracture. It also reduced risk factors by 30% in women with previous vertebral fracture. Future treatments include combinations of above agents and recombinant PTH (rhPTH, 1-34).

This program has been provided through an unrestricted educational grant from McNeil Consumer Healthcare, the makers of TYLENOL*(acetaminophen).