Forteo Not a Substitute for Calcium, Vitamin D Supplements, Study Finds

Routine use of Forteo (teriparatide), a synthetic parathyroid hormone fragment, appears unlikely to effectively substitute for calcium and vitamin D supplements among people with chronic hypoparathyroidism, according to the results of a Phase 3 trial.

The findings were published in a study, “Chronic hypoparathyroidism and treatment with teriparatide,” in the journal Endocrine.

Hypoparathyroidism is characterized by low levels of the parathyroid hormone (PTH). The loss of PTH results in low levels of calcium, phosphate, and vitamin D. Low calcium — a condition called hypocalcemia — can cause muscle cramps, fatigue, and seizures, among other symptoms.

Although calcium and vitamin D supplements are common treatments, their chronic use can lead to long-term complications.

Eli Lilly’s Forteo, used to treat severe postmenopausal osteoporosis, has been proposed as an alternative therapy. This engineered treatment consists of the PTH active region. Recommended doses are based on safety information collected from postmenopausal women, and it had not been tested for hypoparathyroidism in a clinical trial.

A Phase 3 study evaluated the safety and efficacy of two regimens of Forteo — 20 micrograms once daily or twice daily — over three months among 12 adults with chronic and poorly controlled hypoparathyroidism.

The goal was to find a dose of Forteo capable of maintaining normal calcium levels and allowing patients to reduce their use of active vitamin D (calcitriol) and/or calcium by at least 50%.

Participants included seven women and five men. Nine individuals had post-surgical hypoparathyroidism (75%) and three had idiopathic hypoparathyroidism, meaning that its cause was unknown.

All patients began with once-daily Forteo. This, however, proved insufficient to lower calcium and calcitriol supplementation by at least 50%. As such, the participants were switched to the twice-daily regimen after 15 days.

Two individuals experienced mild hypercalcemia — abnormally high calcium — at this dosage and had to be tapered back to the single dose. Two other participants discontinued due to adverse events — bone-joint pain and a mild headache — at weeks nine and 11. Both effects ended upon treatment discontinuation.

At the study’s end, all eight patients receiving the double dose reduced their oral calcium and calcitriol supplementation by 50% or more. Six patients stopped calcium supplementation entirely and seven suspended calcitriol.

Neither of the two individuals who had tapered back to the single daily dose eliminated or lowered their calcium and calcitriol supplements by at least 50%.

Before discontinuing, the remaining two patients eliminated calcitriol entirely. One also eliminated calcium supplementation and the other reduced theirs by 50%.

Calcium levels in the blood fluctuated throughout the twice-daily treatment period. In the first two weeks of the trial, when all participants were taking a single daily dose, eight episodes of hypocalcemia without hospitalization occurred among six patients.

Although mean calcium levels tended to remain stable within the normal range after beginning the twice-a-day portion, oscillations also took place. These included six episodes of mild hypocalcemia among five of the 10 patients who completed the trial, and seven episodes of mild hypercalcemia also among five participants.

Mean blood phosphate levels generally remained within the normal range with both dosing regimens.

One patient experienced an episode of abnormally high phosphate — hyperphosphatemia — during the once-daily treatment and nine such episodes occurred among three patients in the double-dose phase.

Active vitamin D levels increased over the course of treatment, showing a statistically significant difference by the study’s end.

Finally, the participants reported a statistically significant improvement in self-reported quality of life, as assessed with the Short-Form Health Survey, namely the bodily pain, social functioning, and vitality domains.

Despite this, the trial results suggest that Forteo treatment cannot entirely replace calcium and vitamin D supplementation, the scientists said.

Overall, they wrote, “[Forteo] twice daily can be associated with episodes of calcium and phosphate oscillations, and/or adverse events, although, [because of] the small group of evaluated patients, this study does not allow conclusive results.”

“The present study,” the investigators concluded, “conveys an important cautionary message to the endocrinologists for the current use of PTH peptides in [hypoparathyroidism] with dosages above those for which safety data have been collected.”