Does menopause always justify bone density testing?
Anne has new-onset hot flashes, Beth’s mother broke a hip, Carol thinks she’s not at risk, Donna has 6 risk factors. Is bone density testing appropriate?
IN THIS ARTICLE
- 4 case studies
- Drug treatment based on T-scores and risk factors Reasonable options if T-score is borderline
- When is a follow-up in 1 year vital? When is a 2- or 3-year interval safe?
- BMD test techniques, sites, and T-scores
This question begs for a simple yes or no, but it is best answered by asking a second question, “Do I need to know my patient’s bone density to give her the best care possible at menopause?” If the answer is yes, then bone density testing is a must, because there is no other way to know what her bone density actually is.
How, then, does this knowledge affect clinical decision-making?
Our concern, of course, is whether we need to intervene pharmacologically to preserve the strength of the skeleton. Even though bone mineral density (BMD) does not completely account for bone strength, it does determine some 60% to 80% of bone strength, and it is still the best predictor of an initial fracture.
Of immediate concern to the physician caring for a woman entering the postmenopausal period is whether she has sufficient bone mass to withstand the bone loss that estrogen deficiency will impose—without developing a dangerously fragile skeletal structure.
Women start losing bone mass years before menopause. While she is still in her mid-40s, a woman’s spinal bone density begins to diminish due to accumulating dietary calcium deficiency, declining physical activity, and declining estradiol levels. (Unless menopause occurs earlier for any reason, however, bone density in the spine is thought to remain relatively stable from the time peak bone mass is attained, before age 30 in most skeletal sites,1 until the mid-40s.) The exact age at which the proximal femur begins to lose bone is more controversial. Cross-sectional studies have suggested that bone loss may in fact begin in a woman’s 20s, almost immediately after reaching peak bone mass. Others have suggested that bone loss does not begin until later, in her 30s.2
A variety of risk factors are modifiable, but one that we cannot modify—genetics— may play the predominant role in determining peak bone mass. Other factors include nutrition, physical activity, intervening illnesses, medications, and lifestyle factors like smoking and alcohol use.
Expect bone loss with any cause of estrogen decline
Postmenopausal bone loss is inexorable in the absence of estrogen replacement, as well as after stopping estrogen replacement therapy (ERT) or hormone replacement therapy (HRT). If your patient stops ERT or HRT, from a skeletal perspective she has just become postmenopausal again. By measuring her bone density, you can ascertain whether bone loss— which will certainly occur—will further deplete bone mass that is already less than ideal. If so, immediate intervention to prevent bone loss is appropriate.
One key longitudinal study,3 for example, found that perimenopausal women lost an average of 2.3% per year from the spine; postmenopausal women, 0.5%. The authors observed these losses in peri- and postmenopausal women, assessed over an average of 27 months. (Women were classified as perimenopausal if they became postmenopausal during the study.)
Calcium intake of 1,000 mg/day or more does not stop bone loss
In a study designed to evaluate the effectiveness of alendronate compared with placebo in preventing bone loss in women within 3 years of menopause, McClung et al4 found a 3% to 4% bone loss at the end of 3 years in the placebo group, despite total calcium intakes of 1,000 mg per day or more.
Stopping HT merits equal concern
Estrogen deficiency precipitated by stopping hormone therapy is due the same concern as that created by menopause itself. Although the exact rates vary in studies, it is clear that bone loss begins when ERT or HRT stops, just as it does with onset of menopause. Hysterectomized postmenopausal women who received ERT for 2 years were found to have a 4.5% decline in posterior-anterior (PA) lumbar spine bone density and a 1.2% decline in total hip bone density only 1 year after estrogen withdrawal.5 This loss occurred despite calcium supplementation.
Trémollieres et al found a 1.64% per year loss of bone density from the spine for the first 2 years after discontinuing HRT, which was similar to that seen in estrogen-deficient women for the first 2 years immediately after menopause.6 In the Postmenopausal Estrogen/Progestin Interventions (PEPI) trial, women who stopped HRT after 3 years lost bone density at an annual rate of 1.04% from the spine and 1.01% from the hip during 4 years of follow-up.7
A conservative assessment of the rate of bone loss in the first few years after menopause or cessation of hormone therapy is about 1% per year from the spine and proximal femur. At first glance, 1% per year does not appear worrisome. But within 10 years of menopause, at or about the age of only 60, 10% of the bone mass that was present at menopause is gone. In 15 years, at least 15% is gone because of estrogen deficiency.
Unquestionably, many women have stopped ERT or HRT or are choosing not to begin, due to media attention on negative findings from trials such as the combined-continuous HRT arm of the Wo men’s Health Initiative (WHI) and the Heart and Estrogen Replacement Study (HERS-I). Reviews of the National Prescription Audit database and National Disease and Therapeutic Index database confirmed a subsequent marked drop in prescriptions for ERT or HRT,8 despite WHI findings showing that combined-continuous HRT significantly reduces the risk of spine and hip fracture.9
Anne:Onset of hot flashes is a “teachable moment”
“Anne,” a 53-year-old Caucasian woman, has come to see you because of hot flashes that have begun to trouble her since her menstrual periods stopped 8 months ago.
Although she knows that estrogen replacement would help relieve her hot flashes, she is uncertain whether to use it, having heard negative media reports about WHI findings. She has no family or personal history of breast cancer, but is very frightened at even the slightest possibility of increasing her personal risk for breast cancer. She is 5’5” tall and weighs 120 lb. She broke her right wrist in a fall at age 46.
Don’t miss this opportunity!
Though Anne’s visit was prompted by distress over hot flashes, night sweats, and related symptoms of sleep disruption, daytime fatigue, mental lapses, and irritability, it’s a “teachable moment” to discuss osteoporosis prevention and testing. As is typical, her primary desire is relief from hot flashes, yet bone loss is a more serious threat.
If long-term inter vention starts early, bone loss and osteoporosis are preventable; in that context, onset of hot flashes can be seen as a positive force, since they prompted her to seek medical help.
Beth:Concerned because of her mother’s hip fracture
Occasionally a patient will raise the issue of osteoporosis herself. “Beth” is a 49-year-old woman who reports that her last menstrual period 3 months ago was very light in comparison to what she considers normal. Her periods have become irregular over the last year, initially being about 21 days apart, but now 10 to 12 weeks apart. She says she may have noticed an occasional hot flash, but it was not troublesome. She is concerned about the menstrual irregularity and wonders if she is close to menopause.
While she is not psychologically troubled about cessation of menstrual periods, she is concerned about potential bone loss due to estrogen deficiency. With additional questioning, you discover that her mother had a hip fracture.
Carol:Believes her risk low and refuses BMD test
“Carol,” on the other hand, says she doesn’t need bone density testing, because she is not interested in taking any medication to prevent or treat osteoporosis.
If Carol truly will not consider preventive medications, then bone density testing is certainly not indicated. The few patients who refuse to consider medications or testing tend to think their risk is slight. Careful questioning often elicits this belief. They may exercise, avoid cigarette smoke, and consume more than adequate amounts of calcium supplements or dairy products.
Unfortunately, such admirable habits in no way prevent estrogen-deficient bone loss.
Genetically determined low BMD
And no woman can overcome the effects of a genetically determined lower-than-average peak bone density, which may exist without the patient’s knowledge. Without a bone density test, the patient is making an uninformed decision and it is from this perspective that this situation is best approached. Her decision should always be respected, but it is our responsibility to insure that it is an informed decision.
Drug intervention based on T-score
By measuring the bone density at menopause, we can determine if pharmacologic intervention to prevent bone loss needs to start immediately. According to the National Osteoporosis Foundation (NOF) and the American Association of Clinical Endocrinologists (AACE) guidelines, if a woman’s T-score is below -1.5 and she has even 1 other risk factor, pharmacologic intervention is warranted.12,13
This level of bone density is clearly above the threshold for a diagnosis of osteoporosis based on the WHO criteria. Nevertheless, this patient’s estrogen deficiency will further deplete her already lower-than-normal bone density, and could be rapidly devastating. Knowledge of her T-score gives us potential to prevent fractures, now that we have drugs to prevent such devastation.
Three guidelines (TABLE)12-14 recommend pharmacologic intervention if the T-score is -2.5 or lower, and these guidelines differ only in the intervention threshold that also requires an additional risk factor. Note that all 3 recommend pharmacologic intervention when there is only a single risk factor in addition to a bone density level that would not be considered osteoporotic by WHO criteria.
The Food and Drug Administration (FDA) has approved drugs for prevention or treatment of postmenopausal osteoporosis, or both, based on whether data demonstrate that a drug:
- inhibits or stops bone loss, for the prevention indication, or
- reduces fracture risk, for the treatment indication.
The FDA-approved dosages of nonestrogen agents may vary by indication (TABLE). In clinical practice, however, the distinction between prevention and treatment is often less clear, leaving the dosage to the judgment of the clinician.
The complete list of clinical risk factors to consider in initiating therapy based on the T-score is lengthy; furthermore, an ever-increasing number of medications and diseases are now known to contribute to bone loss. The 5 major risk factors listed in the margin below are some of the most important to consider along with the T-score.
Drug intervention is appropriate when there are…
NO RISK FACTORS AND A T-SCORE:
RISK FACTORS AND A T-SCORE:
National Osteoporosis Foundation
American Association of Clinical Endocrinologists
At or below -2.5
-1.5 or poorer
North American Menopause Society
-2.0 or poorer
FDA-approved agents for prevention and treatment of postmenopausal osteoporosis*
5 mg po qd or 35 mg po qw
10 mg po qd or 70 mg po qw
2.5 mg po qd
5 mg po qd or 35 mg po qw
60 mg po qd
*Unless otherwise noted, doses are the same for prevention or treatment
†Although FDA-approved, ibandronate is not currently marketed in the United States
Follow-up testing intervals
Once your patient begins drug therapy, it is appropriate to follow up periodically with bone densitometry. The skeletal site measured at follow-up and the intervals between are dictated by reimbursement, as well as scientific issues. Many insurers, including Medicare, reimburse only once every 2 years.16 Exceptions are few.
From a scientific standpoint, BMD increases at the PA lumbar spine may be sufficiently great to be detected in only 1 year, with potent agents like the bisphosphonates or teriparatide. Since changes in PA lumbar spine density are generally less with raloxifene or salmon calcitonin, waiting 2 years to remeasure the PA lumbar spine is entirely appropriate here.