The response of the skeletal system to parathyroid hormone (PTH) for growth and bone mineralization in the postnatal period is crucially dependent on a full insulin growth factor (IGF)-1 complex, investigators have found.
"Now that anabolic therapy with PTH is widely available for treating osteoporosis, it would be valuable to determine whether presentation of the components of the ternary IGF-1 complex in humans could be used to predict skeletal responsiveness to PTH," the study team notes.
"A full complex of circulating IGF-1 is crucial for a complete anabolic response to PTH and for bone resorption and growth."
Clifford Rosen, from St Joseph Hospital in Bangor, Maine, USA, and co-workers explain in the Journal of Endocrinology that the role of circulating IGF-1 in skeletal growth and in the anabolic response to PTH is not well understood.
Therefore, they studied the effects of intermittent PTH administration on bone remodeling in 12-week old IGF-1-deficient mice that had been generated with gene deletions of either the IGF-1 gene (LID), the acid labile (ALS) gene (ALSKO), both liver IGF-1 and ALS inactivated genes (LA), or no gene deletions (controls).
The mice were injected with either a vehicle (VEH) or 5µg/kg/day of human PTH for 4 weeks.
The researchers demonstrated that the cortical skeleton was "profoundly affected" by IGF-1 deficiency in the mice. Specifically, while ALSKO mice and controls showed cortical bone area increases in response to PTH, LID and LA mice did not.
Moreover, femoral and vertebral bone volume fractions increased in response to PTH in LID, but not in ALSKO or LA mice.
Speaking to Medwire News, Rosen explained: "It is known that ALS is a protein that binds IGF-1 in the circulation; it was never thought to have a role elsewhere, but we found that when we knock out ALS, we get major effects."
He continued: "A full complex of circulating IGF-1 is crucial for a complete anabolic response to PTH and for bone resorption and growth.
"Measurement of IGF-1 alone may not tell you whether a patient will respond to PTH but measuring ALS as well may."
Concluding, Rosen emphasized: "These findings may be useful if applied to the treatment of humans with osteoporosis, as it is crucial to determine which patients may be responders to very expensive PTH therapy."