Osteoporosis treatment advances timely

October 3, 2007

Osteoporosis treatment is becoming more aggressive, and just in time. Loss of bone mineral density (BMD) is already more prevalent than heart attack, stroke and breast cancer combined, said Irene Hamrick, MD, professor at the Brody School of Medicine at East Carolina University, Greenville, North Carolina. Costs associated with osteoporosis have already hit $17 billion annually and continue to climb as baby boomers age and enter higher risk categories.

Osteoporosis treatment is becoming more aggressive, and just in time. Loss of bone mineral density (BMD) is already more prevalent than heart attack, stroke and breast cancer combined, said Irene Hamrick, MD, professor at the Brody School of Medicine at East Carolina University, Greenville, North Carolina. Costs associated with osteoporosis have already hit $17 billion annually and continue to climb as baby boomers age and enter higher risk categories.

"Women can lose up to one-third of their bone mass in the first ten years following menopause," Dr Hamrick said at the American Academy of Family Physicians Scientific Assembly in Chicago on Wednesday. "Age is the most reliable indicator for osteoporosis."

Treatment guidelines in the past generally ignored bone density loss until patients met predefined limits for osteopenia or osteoporosis. Current guidelines call for screening all women at age 65 and women at higher risk at age 60. In addition, Dr Hamrick advised calcium and vitamin D supplementation for all patients at risk for bone density loss regardless of screening status or results. This includes all patients on steroid treatment, all patients in nursing homes or other institutional environments, all postmenopausal women, and all men at risk for bone density loss due to medication or underlying medical conditions, such as low testosterone levels.

Dual energy x-ray absorptometry (DEXA) remains the gold standard for assessing bone mineral density. Results are typically shown as a T-score, a comparison with a standard cohort of 30-year old Caucasian women. Any T-score greater than -1.0 is considered normal. Scores between -1.0 and -2.5 indicate osteopenia. Any score less than -2.5 indicates osteoporosis.

A current trend is to show a Z-score, an age-adjusted comparison of BMD. However, Dr Hamrick said an age-adjusted comparison is useless in assessing a patient?s condition.

Other screening modalities have been used, but none are as reliable as DEXA, she added. Ultrasound, which measures bone density, does not correlate with DEXA scores, but early evidence indicates that it may correlate with fracture risk.

"Ultrasound is an easily accessible screen but it is not very reliable," she cautioned. Since you have to refer all patients in the negative area for DEXA anyway, you may as well start where you will have to go."

Screening options are likely to expand in the future, she added. Bone markers in blood or urine, including N-teleopeptide and alkaline phosphotase are in clinical trials. Homocysteine as a marker for osteoporosis remains experimental.

Treatment options have also expanded recently. Anyone at risk, male or female, young or old, should take calcium, 1000 to 1500 mg/d. Dietary calcium is poorly absorbed, Dr Hamrick noted, which makes supplementation necessary. She usually recommends calcium carbonate as the richest source of elemental calcium. Because calcium absorption is limited, she recommended three daily doses of 500 mg.

Patients at risk for bone density loss should also take between 600 IU and 1000 IU of vitamin D daily. Studies show that the recommended daily dose, 400 IU, is not effective at preventing fractures.

"You need 800 to 1000 IU daily to inhibit fractures and falls," she said. Only 18% of patients with hip fractures receive appropriate drug therapy for bone loss, Dr Hamrick continued. Estrogen is effective in reducing fractures, but is generally not recommended due to associations with increased cardiovascular events. Raloxifene has been shown to reduce fractures in the spine, but seems to have no effect on hip fractures.

Calcitonin also protects against spinal fractures but has no effect on hip fracture rates. It is, however, useful in pain control for patients with hip and other fractures. The analgesic effect takes about two weeks to appear for most patients.

Bisphophonates remain first line treatment for BMD loss. All products in the class inhibit osteoclast activity, allowing osteoblasts to lay down new bone.

Alendronate has been shown to reduce hip and spinal fractures, but has GI side effects. Risedronate has fewer GI side effects. Ibandronate can be taken once monthly as an oral formulation or once every three months via IV. The IV formulation is somewhat more effective, possibly because supervised, according to Dr Hamrick.

The newest agent is zoledronic acid, recently approved for acute hypercalcemia associated with cancer. It is given intravenously once yearly. Parathyroid hormone is also effective in reversing bone loss when given in 60-minute pulses. The first 60 minutes of exposure stimulates osteoblasts, Dr Hamrick explained, but further exposure stimulates osteoclasts and results in further bone loss.