Parathyroid Hormone Nasal Spray Shows Promise Against Osteoporosis

Peggy Peck

October 06, 2004

Oct. 6, 2004 (Seattle) -- Early clinical results indicate that an investigational once-daily nasal spray of parathyroid hormone stimulates the growth of healthy bone quickly with results comparable to injectable forms of the hormone, according to lead investigator Toshio Matsumoto, MD, professor and chairman of the department of medicine and bioregulatory sciences at the University of Tokushima Graduate School of Medicine in Japan.

"We believe that because nasal hPTH(1-34) increases bone formation while reducing bone resorption, it makes it a promising candidate for the treatment of osteoporosis," said Dr. Matsumoto.

In an oral presentation here at the 26th annual meeting of the American Society for Bone and Mineral Research (ASBMR), Dr. Matsumoto said that the parathyroid compound, being developed by Chugai Pharmaceutical Co., Ltd., of Tokyo, Japan, resulted in significant bone mineral density (BMD) increase compared with baseline at three months using the 1,000 µg dose of the recombinant hormone.

In the study, 92 osteoporotic women aged 52 to 84 years were enrolled. The women were randomly assigned to receive either 250 µg (PTH250, n = 31), 500 µg (PTH500, n = 30), or 1,000 µg (PTH1000, n = 31) of daily nasal hPTH(1-34) spray for three months. In addition, all participants received supplemental calcium (300 mg) and 200 IU of vitamin D daily.

After three months, in the 31 women with osteoporosis who received the highest dose, lumbar spine BMD had increased by 2.4% compared with baseline measurements ( P < .05). There were insignificant BMD increases among the women randomized to the 250-µg or 500-µg doses.

Dr. Matsumoto said the nasal spray device is designed to deliver a precise dose of the drug. The patient sprays each nostril once a day. He said it does not matter what time of day the spray is delivered.

"While there are numerous products on the market that are designed to prevent the loss of bone in persons with osteoporosis or at risk of osteoporosis, only parathyroid hormone stimulates bone formation," Dr. Matsumoto told Medscape. "However, it is somewhat paradoxical that a constant infusion of parathyroid hormone actually can result in bone resorption."

He noted that the pharmacokinetics of hPTH(1-34) trigger an initial spike in drug concentration -- known to stimulate bone growth -- followed by a rapid decrease of the hormone in the blood, which would limit the resorption reaction. The serum level of hPTH(1-34) reaches 300 pg/mL within 15 minutes after release of the nasal spray into the nostrils, but it declines to less than 100 pg/mL by the end of one hour.

In addition to the BMD increases seen with nasal parathyroid hormone administration, Dr. Matsumoto noted that markers of bone formation also increased in a dose-dependent fashion.

The currently approved parathyroid hormone -- Forteo -- is delivered by daily subcutaneous injection, Dr. Matsumoto said. "That delivery system results in low compliance due to its invasive and self-injectable formulation," he said. Previous attempts at the use of a nasal spray with parathyroid hormone have led to a suggestion of unwanted bone or calcium growths in the nose. Dr. Matsumoto said that his researchers carefully monitored that possibility as well as serum calcium levels and saw no indication of that adverse event in either animal models or in patients.

"The development of this nasal spray of parathyroid hormone is very exciting," said Clifford Rosen, MD, a former president of the ASBMR. "Everyone is looking for ways to reduce costs and increase compliance with this treatment," he told Medscape.

Dr. Rosen, director of the Maine Center for Osteoporosis Research in Bangor, said that physicians will be closely following progress of the spray. "If it works and these early results can be confirmed and improved upon, it would be spectacular." Dr. Rosen was not involved in the study.

Dr. Matsumoto estimated that there would be at least two more years of clinical trials before the drug is considered for licensing. However, he said that if all the trials have positive results, the product might be ready for the general market before the end of this decade.

ASBMR 26th Annual Meeting: Abstract 1171. Presented Oct. 4, 2004.

Reviewed by Gary D. Vogin, MD


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