Premenopausal women face bone loss after stopping teriparatide

By Joan Stephenson

Premenopausal women with idiopathic osteoporosis who add bone through use of teriparatide begin to lose bone once the drug is discontinued and thus may require antiresorptive therapy for maintenance, a small study shows.

The study builds on a previous open-label pilot study in which 21 premenopausal women with idiopathic osteoporosis received teriparatide for 18 to 24 months to increase bone mineral density (BMD).

"In postmenopausal women and older men with osteoporosis, treatment with teriparatide must be followed with an antiresorptive drug to maintain the gains from teriparatide," Dr. Elizabeth Shane, of Columbia University in New York, told Reuters Health by email.

"It was not known whether this is also true of premenopausal women who are still making estrogen, which could act as a natural antiresorptive agent and might prevent bone loss," she said.

BMD for women in the open-label trial increased substantially, with gains of about 10.8% at the lumbar spine, 6.2% at the total hip, and 7.6% at the femoral neck.

To investigate whether premenopausal women maintained teriparatide-associated BMD gains, the researchers measured BMD in 15 of the original study participants about two years after the women stopped taking the drug.

The women, who were taking no bone-active therapy (other than oral contraceptives taken by five of them), experienced a significant 4.8% decrease in BMD at the lumbar spine, but BMD remained stable at the femoral neck and total hip, the researchers reported online September 10 in the Journal of Clinical Endocrinology & Metabolism.

Most of the women still had more bone than before they had started taking teriparatide, which "could be partially due to their ability to make their own estrogen," Dr. Shane said.

Bone loss after teriparatide cessation was highly variable, but women who lost bone tended to have larger gains during teriparatide treatment and had evidence of higher bone turnover. In addition, the amount of bone loss appeared to be greatest in women older than 40.

"These findings lead us to think that the estrogen secreted by a premenopausal woman's own ovaries may not be enough to prevent waning of the effect of teriparatide after it is stopped, particularly in older women, who may not make as much estrogen as younger women," Dr. Shane said.

"It also suggests that doctors should consider following teriparatide with an antiresorptive drug in premenopausal women, particularly if they are older than 40," she added.

"This study provides useful information and is of value in determining the most suitable approach to the treatment of osteoporosis in premenopausal women," Dr. Aliya Khan, of McMaster University in Hamilton, Ontario, Canada, told Reuters Health by email. "Those women who are treated with teriparatide do require ongoing follow-up and monitoring to ensure that bone loss does not occur following cessation of therapy."

Larger studies are needed to determine the best treatment strategy for women younger than 50 who are still premenopausal and are experiencing fragility fractures, Dr. Khan said.

Dr. Shane said her research group has a new trial under way in which premenopausal women who have completed up to two years of teriparatide therapy will have the option to take a newer antiresorptive drug, denosumab, for two years.

"Denosumab, when used as a follow-up therapy after teriparatide, has been shown to increase bone density even further in postmenopausal women," she said. "We are testing whether this will also be true in premenopausal women."

Eli Lilly provided partial support for this research through Columbia University and has relationships with three coauthors.

SOURCE: http://bit.ly/1NNMRTV

J Clin Endocrinol Metab 2015

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