How long should treatment continue?
The practical clinical problem is that when patients ask: “Doctor, how long do I need to take my bone medicine?” they are not emotionally prepared to hear, “Forever.”
It is probably better to say that it’s important to stay on treatment at least 1 to 2 years, and adhere closely to the regimen. When follow-up testing is obtained, the results can influence the next recommendation—which is likely to be that treatment should continue at least 1 or 2 more years. This pattern is more likely to ensure that the patient has high morale and follows the regimen.
Bone mass accrues as treatment continues
Bone HG, Hosking D, Devogelaer JP, et al. Ten years’ experience with alendronate for osteoporosis in postmenopausal women. N Engl J Med. 2004;350:1189–1199.
In postmenopausal women with osteoporosis (n = 86) who were treated for 10 years with alendronate, 10 mg daily, hip and spinal bone density continued to increase throughout follow-up.
Women who stopped therapy gradually lost bone density. After 10 years of alendronate, the increase in bone mineral density was 14% at the lumbar spine and 10% at the hip trochanter.
Studies have demonstrated that bone density continues to increase with up to 10 years of therapy with alendronate.
Alendronate halts bone loss after stopping estrogen
Ascott-Evans BH, Guanabens N, Kivinen S, et al. Alendronate prevents loss of bone density associated with discontinuation of hormone replacement therapy. Arch Intern Med. 2003;163:789–794.
Postmenopausal women (n = 144) who had recently discontinued estrogen therapy were randomized to receive a placebo or alendronate, 10 mg daily. After 1 year, the alendronate group had a 2.3% increase in spinal bone density; the placebo group, a 3.2% decrease.
Once drug therapy stops, bone density begins to decrease—more rapidly after estrogen than after bisphosphonates. In women who stop estrogen, initiation of alendronate blocks bone loss that will otherwise occur. Therefore, women with osteopenia or osteoporosis who stop estrogen therapy should consider starting an alternative bone medicine.
How should you monitor treatment?
Nurses improve adherence
Clowes JA, Peel NFA, Eastell R. The impact of monitoring on adherence and persistence with antiresorptive treatment for postmenopausal osteoporosis: a randomized controlled trial. J Clin Endocrinol Metab. 2004;89:1117–1123.
In this study, 75 postmenopausal women with osteopenia on raloxifene treatment were randomized to 3 different monitoring regimens: no monitoring, nurse interactions with the patient to ensure treatment compliance, or monitoring of urinary markers of bone turnover.
The patients who had the best adherence to therapy had the greatest increase in bone mineral density.
Adherence increased by 57% in the nurse interaction group compared to no monitoring. Measuring urinary markers of bone turnover did not improve adherence or persistence with therapy compared to nurse interactions.
Nurse monitoring of treatment adherence appeared worthwhile, in this comparison of monitoring methods. In routine clinical practice, there is seldom a need to measure markers of bone turnover in women taking bisphosphonates.
Densitometry every 2 years
Greenspan SL, Resnick NM, Parker RA. Combination therapy with hormone replacement and alendronate for prevention of bone loss in elderly women. JAMA. 2003;289: 2525–2533.
A total of 373 women over age 65 were randomized to placebo, conjugated equine estrogen 0.625 mg daily, alendronate 10 mg daily, or both estrogen and alendronate. After 3 years, increases in spinal and hip bone density were greatest in the alendronate plus estrogen group. Alendronate alone was slightly better than estrogen alone in improving bone density at the hip. Alendronate and estrogen were similarly efficacious in improving spine bone density. All active regimens were superior to placebo.
In my practice, I measure bone density every other year to assess response to antiresorptive therapy. Since bone turnover is slow, more frequent measurements are seldom warranted. If bone density stabilizes or increases, I continue therapy.
If bone density decreases significantly on standard monotherapy, I would consider adding estrogen and repeating bone mineral testing in 1 year.
I would also check for secondary causes of bone disease by measuring serum thyroid-stimulating hormone, calcium, albumin, PTH and 25-hydroxyvitamin D.
Alternatively, a woman who has lost bone density on monotherapy can be referred to an endocrinologist.
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