Studies explain how drugs for asthma, diabetes cause osteoporosis
LATELY things have not been going smoothly for Koel Dutta. A homemaker in Kolkata, the 38-year-old has asthma.
Doctors have put her on Pediapred—a class of glucocorticoid steroids—for the past one year. Since January, Dutta was getting fractures easily. Once she tripped on the doorstep and fractured her wrist. The next time she fractured her lower spine while lifting a heavy bucket. Worried about her condition, doctors asked Dutta to get a bone mineral density test done.
Her neighbour Ishan Kumar also got a bone scan. The 48-year-old tax consultant is suffering from epithelial tissue cancer for the past one year and has been prescribed Dexamethasone Intensol—another class of glucocorticoid steroids. Test results revealed both Dutta and Kumar have osteoporosis. Sabyasachi Sen, physician at the Gamma Centauri Nursing Home in Kolkata, said taking glucocorticoid pills for more than three months raises the risk of osteoporosis.
To avoid the bone loss disease Sen recommends daily doses of calcium and vitamin D supplement along with weight exercise for at least 30 minutes for those who are on long-term glucocorticoid medication.
Two independent studies by scientists at University of Texas Southwestern Medical Center in USA and Fritz-Lipmann Institute in Germany support Sen’s diagnosis. They recently shed light on why some commonly used drugs can increase one’s odds of breaking bones.
Glucocorticoids, a class of steroid hormones, play a vital role in the treatment of ailments like asthma, arthritis and gastrointestinal diseases. High glucocorticoid levels in the body interfere with the absorption of calcium from the intestine. As a result, the body seeks out calcium from the bones and causes osteoporosis.
This is not all, said the team led by Jan Tuckermann of the Fritz-Lipmann Insti tute. High glucocorticoid levels also hinder bone formation. Bone is a dynamic tissue—it constantly remodels through a careful balance between the activities of bone-building osteoblast cells and bone-destructing osteoclast cells. Osteoporo sis occurs when destru ction outpaces formation. The team conducted experiments on mice and cultured cells. Glucocorticoid binds to its receptor present in almost every cell in the body and enters the cell. Together they supress the activity of a protein-forming factor, AP-1, which controls the activity of osteoblasts, the scientists observed. This inhibits the rate of bone formation and leads to osteoporosis, they reported in the journal Cell Metabolism on June 9.
The mice in whose body scientists had suppressed glucocorticoid receptors did not show bone loss. “Our research suggests that selectively acting glucocorticoid that spares AP-1 could protect the bone while still helping asthma patients,” said Tuckermann. Another study lead by Yihong Wan from University of Texas South western Medical Center focused on a drug, Rosiglitazone, recommended to diabetics. Exce ssive use of the drug also leads to increased fractures.
The drug combines with a receptor, PRARg, present on the cell membrane. Together they activate a protein PGC1b, which, in turn, works with estrogenrelated receptors to stimulate the formation of osteoclast cells. “Deletion of PGC1b has been found to confer complete resistance to Rosaglitzoneinduced bone loss,” Wan noted in the same journal.
Hope for advanced drugs
Early effects of glucocorticoids on bone can be reversed by the administration of bisphosphonates, a class of drugs, said Ernesto Canalis from Saint Francis Hospital and Medical Centre, Hartford, USA. Parathyroid hormone, which increases the concentration of calcium in the blood, can also help reverse the inhibitory effects of glucocorticoids on bone formation, Canalis added.
Yasuhiro Tamura, endocrinologist at Teikyo University School of Medicine in Japan said genistein, a hormone in soy food, can also protect bones from the effects of osteoporosis. Wan assures that based on her study, it is possible to design advanced diabetes drugs that would not cause osteoporosis.
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