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Growth Hormone May Be Novel Therapy for Very Rare Bone Disease

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Wednesday, November 08, 2017

NEW YORK - Recombinant human growth hormone (rhGH) is a potential novel therapy for fibrogenesis imperfecta ossium (FIO), a very rare but disabling and ultimately fatal bone disease, a small study from India suggests.

First described in 1950, FIO is an adult-onset, progressive disease that can be mistaken for axial osteomalacia. Diagnosis is often delayed, and the majority of patients are bed-bound at the time of diagnosis.

FIO manifests clinically with generalized bone pain and multiple fractures of both the axial and appendicular skeletons. Routine biochemical measures are normal, except for an elevated serum alkaline phosphatase.

The underlying abnormality in FIO appears to be an acquired defect in bone collagen fibrillary arrangement. The pathogenesis is unknown and no effective therapy has yet been identified, although vitamin D, malphalan, steroids, bisphosphonate, testosterone, and other drugs have been tried.

rhGH is known to have an osteoanabolic effect and has been used with some success to treat osteoporosis and a specific type of osteomalacia. The researchers therefore decided to try rhGH therapy in two brothers under their care.

Patient 1 was a 48-year-old Indian man who presented with a 10-year history of generalized bone pain, multiple fractures, and muscle weakness and was bed-bound at the time of presentation. He appeared to have a family history of FIO, his mother and maternal uncle having died of a “disabling bone disease.”

He was found to have an elevated serum alkaline phosphatase, a pseudo-fracture of the right scapula, multiple rib fractures, bilateral coxa vara, and femoral neck fractures.

His younger brother, Patient 2, presented at age 38 with an almost identical history, with backache and generalized bone pain for six to eight years. A year before presentation, he had sustained a fracture of the right femoral neck with dislocation. He later sustained fractures of the shafts of the left humerus and left femur with consequent skeletal deformities, leading to his being bed-bound.

Both men had been treated with oral calcium 500 mg twice a day and vitamin D 60,000 IU per month for more than two years, without noticeable improvement.

The researchers diagnosed both with FIO and began treatment with rhGH 1 IU daily at bedtime. Calcium and vitamin D were continued.

Within three months, both men began to notice symptomatic improvement, with further clinical improvement by the end of one year. Bone pain resolved enough in both patients to allow them to perform most of their activities of daily living.

All fractures healed, and contractures improved with physiotherapy, though deformities persisted. Bone biopsies showed “dramatic improvement” in mineralization.

In a report online February 28 in the Journal of Clinical Endocrinology and Metabolism, the authors conclude that rhGH “offers a potential novel therapy for FIO” and could be used long-term.

The older brother remained on daily rhGH therapy for more than four years since the initial year of treatment (though more recently has received it only intermittently because of financial issues), is doing well and able to carry out activities of daily life, and has experienced no side effects, Dr. Sanjay Kumar Bhadada, of the Postgraduate Institute of Medical Education and Research, Chandigarh, India, told Reuters Health by email.

The younger brother, unfortunately, was lost to follow up after discharge from the hospital, according to Dr. Bhadada.

FIO is an ultra-rare skeletal disorder in which the collagen matrix (on which bone mineral is deposited) is disorganized, Dr. Matthew Drake of the Mayo Clinic told Reuters Health in an email, adding that no recognized therapy exists.

Whether this study’s findings will extend to other patients with FIO is uncertain, Dr. Drake cautioned, particularly because the subjects were brothers, “and thus may have had an unrecognized genetic basis for their disease which might be absent in others with FIO.”

In addition, he commented, “whether rhGH can be used long-term is unclear, as we know that long-term exposure to high levels of growth hormone in adults may lead to adverse outcomes,” such as an increased risk of diabetes, increased bone growth leading to joint abnormalities and increased pressure on nerves, which can result in carpal tunnel syndrome.

Author: Scott Baltic
Source: www.medscape.com
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