Osteoporosis

Are you assessing risk and discussing new treatments for osteoporosis?

Chief, Department of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts

Dr Barbieri reports that he has served as a consultant to Novartis and Combinent BioMedical Systems.

Who is at greater risk of osteoporotic fracture: Patient A or B?

Patient A is a 60-year-old Caucasian woman, 8 years postmenopausal, with a family history of osteoporotic fracture. She takes thyroxine for hypothyroidism and is otherwise healthy. Her height is 63 inches and her weight is 135 pounds. Dual-energy x-ray absorptiometry (DXA) demonstrates a T-score of –2.2 at the femoral neck and lumbar spine. She has no personal history of low-impact fracture.

Patient B has the same clinical history and test results as Patient A, except Patient B reports having had one low-impact fracture.

What is the absolute risk of osteoporotic fracture and hip fracture for these 2 women over the next 10 years? Which patient has a greater risk of osteoporotic fracture over the next 10 years? Who should be offered treatment?

How to decide which patient needs screening?

For many years, authorities have recommended that postmenopausal women at high risk of fracture, especially women with a T-score less than or equal to –2.5 at the lumbar spine or hip, be offered osteoporosis treatment. Greater controversy has surrounded the guidelines for the approach to women with low bone mineral density (BMD; T-score between –1.5 and –2.5). These women are at a low absolute risk of frac-ture, but a significant percentage of all osteoporotic fractures occur in this group.^1,2

In early 2008, the World Health Organization (WHO) and the National Osteoporosis Foundation (NOF) released a quantitative risk assessment algorithm to guide therapy decisions. New treatment guidelines are based on calculated 10-year absolute risk estimates for fracture.

The new risk assessment algorithm and accompanying treatment guidelines do not significantly change the approach to postmenopausal women with a T-score less than or equal to –2.5. These women should still be offered treatment as previously recommended. But the approach to women with a T-score between –1.5 and –2.5 has changed. The new WHO algorithm will identify some of these women as being at high absolute risk for fracture, and others at low risk. Therapy decisions are guided by this new quantitative approach to risk assessment.

Past and present: Summary of NOF guidelines

Prior to 2008, NOF guidelines used T-score and clinical risk factors to provide guidance on which patients to treat with a bone medicine. Postmenopausal women with the following clinical characteristics were typically recommended for treatment with a bone medicine: a lumbar spine or hip T-score of –2 or less or a lumbar spine or hip T-score between –1.5 and –2.0 with risk factors.

The new NOF guidelines alter the approach for women with low bone density and a T-score between –1.0 and –2.5.

New WHO algorithm for estimating fracture risk

Three variables are of paramount importance in determining the risk of osteoporotic fracture: (1) age, (2) BMD, and (3) personal history of previous fracture. Other important factors are: weight and height, history of glucocorticoid therapy, cigarette use, consumption of more than 3 alcoholic drinks per day, history of hip fracture in a parent, history of rheumatoid arthritis, and history of diseases that cause secondary osteoporosis. By incorporating all of these factors in a quantitative risk assessment algorithm, it may be possible to identify those women with low bone mass who would benefit most from treatment with a bone medicine.

Key Bone Density Definitions

The new WHO and NOF algorithm for assessing fracture risk incorporates all of these factors in order to calculate 10-year absolute risk estimates for hip fracture and all-site major osteoporotic fractures. The World Health Organization Fracture Risk Assessment Tool is accessible at many Internet sites, including www.shef.ac.uk/FRAX. The new NOF guidelines do not alter the long-standing recommendation that therapy be offered to women with a BMD T-score of –2.5 or less at the femoral neck, total hip, or lumbar spine.

The new NOF guidelines recommend that therapy be offered to women who are older than 50 years and have a 10-year probability of hip fracture of greater than or equal to 3% or a 10-year overall major osteoporotic fracture risk greater than or equal to 20%. These threshold levels for treatment are based on a careful assessment of the benefits, risks, and costs of therapy in a United States population.^3,4

Based on the WHO fracture risk assessment tool, Patient A has a 10-year risk of hip and overall fracture of 2.2% and 14%, respectively. Patient B has a 10-year risk of hip and overall fracture of 3.1% and 24%, respectively. With the new guidelines, Patient B should be offered treatment with a bisphosphonate. Patient A probably does not need treatment with a bone medicine.

How will the new WHO algorithm and NOF guidelines influence your practice?

As noted above, for postmenopausal women with a T-score of –2.5, there are no major changes to previous treatment recommendations. The expert consensus is that those women with established osteoporosis will benefit from being offered osteoporosis treatment.

The major changes will be for women with low bone density (intermediate T-scores). The new WHO algorithm provides a more precise quantitative risk assessment. The new risk assessment algorithm and guidelines will likely result in fewer patients younger than 65 years with low bone mass being selected for treatment.⁵

Limitations of the WHO and NOF algorithm

There are no large-scale trials specifically utilizing the new guidelines for the selection of patients for osteoporosis treatment. Future trials and evolving perspectives on the cost-benefit of osteoporosis treatment at various rates of fracture risk may result in modifications to the guidelines. Where resources are limited, the threshold for recommending therapy may be higher than in regions with substantial resources. The cost- benefit analysis for the United States assumed that osteoporosis therapy costs approximately $600 per year. If these costs were to decrease to $100 annually, it could change the cost-benefit analysis and potentially increase the number of patients who are offered therapy. Recently, large retail outlets have significantly reduced the cost of some osteoporosis medicines. This may influence future risk-benefit-cost assessments.

The WHO algorithm is not designed to provide guidance for the treatment of patients with low bone mass at the spine but normal bone at the hip because the spine T-score is not utilized for risk assessment. In general, the previous NOF guidelines can be utilized to individualize therapy in these situations. Also, the WHO algorithm does not explicitly recognize additional high-risk situations, such as women with premature ovarian failure (time since menopause is not a component of the calculation), women with an eating disorder, and women using aromatase inhibitors, a commonly used medicine that is known to cause bone loss. Individualization of care remains a cornerstone of osteoporosis treatment.

Diagnosis, prevention, and treatment: Clinical pearls

Treatment recommendations should be tailored to each patient. Among postmenopausal women older than 50 years, general recommendations for prevention and treatment of osteoporosis include:

Screening. Recommend BMD testing for women aged 65 years or older or for women aged 50 to 65 years if there is a clinical concern or risk factor(s). Recommend BMD testing for postmenopausal women who have a low-trauma fracture.

Calcium and vitamin D. Recommend adequate amounts of vitamin D (800 IU daily) and calcium (1200 mg daily). Vitamin D supplementation at a dosage of 800 IU daily is more likely to reduce the risk of fracture than a dosage of 400 IU daily, the standard recommended dietary allowance.⁶

Lifestyle modification. Increase aerobic and muscle strengthening exercises, cease tobacco use, and limit the use of alcohol to no more than 1 alcoholic beverage per day.

Treatment. In general, postmenopausal women between 50 and 60 years of age, with low bone mass, no previous history of fracture, and no clinical risk factors, do not need treatment with a bone medicine.⁷

Initiate treatment for women with a BMD T-score of –2.5 or less at the femoral neck, total hip, or lumbar spine.

Initiate treatment for women with a low bone mass and a 10-year hip fracture probability of 3% or more or an overall fracture risk of 20% or more, as calculated by the WHO Fracture Risk Assessment Tool.

Follow-up and long-term management for at least 5 years

The most widely used bone medications are the bisphosphonates: alendronate, risedronate, ibandronate, and zoledronate. Other FDA-approved bone medicines include estrogen or estrogen-progestin hormone therapy, raloxifene, parathyroid hormone, and calcitonin.

Follow-up. After initiating a bone medicine, a DXA BMD can be measured in 1 to 2 years to assess changes in bone density. If the bone density is stable or increases, continue therapy. If bone density decreases significantly, assess compliance with treatment. If compliance with treatment has been good and bone density was demonstrated to significantly decrease with treatment, consider a new regimen and reassess bone density in 1 to 2 years. An alternative approach is to measure fasting urinary cross-linked N-telopeptides of type I collagen (NTX) or serum type I collagen C-telopeptides (CTX) before and 3 to 6 months after starting antiresorptive treatment, such as a bisphosphonate. If the marker has decreased by 50% or more, treatment is likely to be successful and bone density can be assessed in 2 years. If the marker has not decreased by 50%, noncompliance or incorrect dosing, such as taking the bisphosphonate with food, are likely causes of a poor marker response.

Complications. Osteonecrosis of the jaw is a rare complication of oral bisphosphonate therapy in postmenopausal women who do not have cancer. For women who have taken a bisphosphonate for 3 years or less, the American Association of Oral and Maxillofacial Surgeons (AAOMS) does not recommend discontinuing treatment prior to invasive dental procedures. However, for women who have taken a bisphosphonate for more than 3 years, the AAOMS recommends cessation of bisphosphonates for 3 months prior to invasive dental surgery. The bisphosphonate can be restarted once the bone has healed.

Long-term management. Treat patients with established osteoporosis for at least 5 years. If after 5 years of treatment the patient is at low risk of fracture, consider discontinuing treatment. If the patient continues to be at high risk of fracture, recommend continued treatment.⁸

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