MENOPAUSE

The WHO algorithm and revised NOF guidelines are expected later this year.

New paradigm will shift focus to older women

This revised approach will shift the focus of therapy from young postmenopausal women at low fracture risk toward older women who do not have osteoporosis but do have an increased risk of fracture by virtue of their age and other factors.⁸ This will direct therapy more appropriately to patients who stand to gain the most and in whom therapy has been proven to reduce fracture risk.

Despite concerns, bisphosphonates appear to be safe for the long term

Bisphosphonates are the most extensively studied and widely used treatment for osteoporosis. Alendronate, the first bisphosphonate approved for the treatment of osteoporosis in the United States, has been available for more than 11 years. In general, all 3 of the currently approved bisphosphonates are well tolerated, and studies following patients for 7 to 10 years have not demonstrated significant adverse events or evidence of skeletal harm with long-term use.^9-11 However, because the drugs accumulate in the skeleton, there is a theoretical concern that long-term use will lead to over-suppression of bone turnover.

Small series of patients receiving bisphosphonates have described unusual fractures, evidence of low formation, and poor fracture healing, suggesting skeletal harm in at least some patients.¹² Bone biopsies performed in patients who received alendronate for 10 years or risedronate for 5 years showed evidence of bone remodeling in all the biopsy samples.^11,13 There was no progressive inhibition of bone metabolism in those biopsies compared with biopsies taken from patients who had received shorter-term treatment.

These findings are consistent with bone-turnover marker data suggesting no progressive suppression of bone turnover with continued use.^10,11,13 Biochemical indices of bone resorption are reduced to the lower half of the normal premenopausal range within about 3 months of beginning therapy, and values remain at that new level as long as patients receive the drug.

Risk of osteonecrosis of the jaw is low in general population

Woo SB, Hellstein JW, Kalmar JR. Narrative review: bisphosphonates and osteonecrosis of the jaws. Ann Intern Med. 2006;144:753–761.

Bilezikian JP. Osteonecrosis of the jaw—do bisphosphonates pose a risk? N Engl J Med. 2006;355:2278–2281.

An association between bisphosphonate therapy and nonhealing lesions of the jaw (so-called osteonecrosis of the jaw) has been observed, but primarily affects patients with cancer-related bone diseases who receive high doses of intravenous therapy in addition to chemotherapy. Patients receiving oral doses of bisphosphonates for osteoporosis in Paget’s disease have also had these lesions, as Woo and colleagues point out.

There is much that we do not know about this clinical problem, including its pathogenesis, whether the risk increases with longer-term use, and whether stopping therapy reduces the risk of developing lesions or improves the outcome of lesions already present. We do know that the incidence of exposed bone in the jaw in patients receiving bisphosphonate therapy for osteoporosis is low, estimated to range from 1 in 1,000 to 1 in 100,000 patients, according to Bilezikian.

Risk is very small, compared with potential benefits

It is important to put this risk in perspective. Based on data from the alendronate Fracture Intervention Trials (FIT), we have estimates of hip and spine fracture risk in certain types of patients. For example, for women age 68 with a femoral neck T-score of –2.5 or lower and no vertebral fractures, the likelihood of a clinical fracture over a mean treatment interval of 4.2 years was 19.6%.¹⁴ In women age 71 with a femoral neck T-score of –2.5 and 1 or more vertebral fractures, spine and hip fractures occurred in 15% and 2.2% of subjects, respectively, over 2.9 years.¹⁵ In these populations, alendronate reduced the risk of both hip and spine fracture by about 50%. For women without a vertebral fracture, the absolute reduction in the risk of clinical fracture over 4.2 years was 6.5% (number needed to treat [NNT]=15). In patients with a vertebral fracture, the absolute reduction in the incidence of further spine and hip fracture was 8.6% over 2.9 years (NNT=12).

This information argues strongly that the concern about osteonecrosis of the jaw does not justify withholding bisphosphonate therapy from patients with osteoporosis. The risk of such lesions in otherwise healthy patients with osteoporosis is very low (much lower than the risk of fracture), and most lesions heal spontaneously when treatment is stopped.

Clinical recommendations

For patients using or considering bisphosphonate therapy for osteoporosis, the following measures may be helpful:

• Have regular dental checkups and routine preventive dental care.
  
• If invasive dental procedures are planned, such as tooth extraction or implants, complete the dental work and allow the bone to heal before beginning bisphosphonate therapy.
  
• If a patient on bisphosphonate therapy plans invasive dental work, stop treatment for 3 months before the procedure and do not restart it until the jaw lesion is healed. Although there is no firm evidence that this strategy is helpful, it is certain that discontinuing bisphosphonate for a few months does not harm the skeleton.
  
• If a patient on bisphosphonate develops exposed bone, stop the drug and consult a dentist or oral surgeon experienced in the care of these lesions.