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Mass General Researchers Develop New Oral Compound for Osteoporosis Prevention and Treatment

In This Article

  • Osteoporosis can be treated with parathyroid hormone-based medications that stimulate bone formation, but these must be administered by daily injection
  • Massachusetts General Hospital researchers identified a new compound that influences components of the parathyroid hormone signaling pathway
  • The compound increased bone formation and bone mass when given orally to mice, which could be further developed and optimized to treat patients with osteoporosis

There is a need for more convenient osteoporosis treatments; currently, there are no available oral medications that stimulate bone formation. Parathyroid hormone-based medications can stimulate bone formation but must be administered by daily injection to be effective.

Massachusetts General Hospital researchers have identified a new compound that increased bone formation and mass when given orally to mice. Their findings hold promise for a new, more convenient therapy for the prevention and treatment of osteoporosis. Senior author Marc Wein, MD, PhD, an endocrinologist in the Endocrine Unit at Mass General, and colleagues describe the study in PNAS.

Identifying the Compound

The investigators first generated a novel structural model of two enzymes that regulate bone growth and remodeling: salt-inducible kinase isoforms 2 and 3 (SIK2 and SIK3). They then utilized a structure-based drug design and iterative medicinal chemistry to identify a compound that inhibits those enzymes.

The compound was termed SK-124 and had parathyroid hormone-like effects when given to cells.

Promising Results in Mice

SK-124 was given orally to mice once a day for three weeks. After the three weeks of oral treatment, the researchers report increased blood levels of calcium and vitamin D, and most importantly, increased bone formation and bone mass. There was no evidence of short-term toxicity.

Based on the findings, molecules like SK-124 may represent an innovative new bone-building therapy for osteoporosis. The researchers are working to further develop and optimize SK-124 into a viable treatment for patients.

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