PTHrP

Where it comes from

Made in

Nearly every tissue in development; in adults the breast, placenta, smooth muscle, and the tumours that make it

Sent out by

Local, not into blood in health; lactating breast puts it into milk and blood

Acts on

• Growth-plate cartilage
• Bone
• Kidney
• Developing teeth and breast
• Placenta (calcium transport)

What it does

• Keeps growth-plate cartilage cells dividing so bones lengthen
• Needed for teeth to erupt and the nipple to form
• Frees calcium from the mother’s bones for milk
• Relaxes smooth muscle in uterus and vessels

In medicine

• The usual cause of humoral hypercalcaemia of malignancy, from squamous, kidney and breast cancers; measured when a cancer patient has high calcium with low PTH ³
• Abaloparatide, a PTHrP (1-34) analogue, has been approved for osteoporosis since 2017; it cut new vertebral fractures from 4.2 % to 0.6 % over 18 months ¹²

Beyond the body’s own use

• A skin patch of abaloparatide was taken into phase 3 to replace the daily injection and failed: it raised spine bone density less than the injection did, and was not approved ⁴
• Its boxed warning about osteosarcoma and its two-year limit, both inherited from rat studies of PTH, were removed in 2021 ²
• Blocking PTHrP in cancer is an old idea that has never produced a medicine; the high calcium of malignancy is still treated with fluids, bisphosphonates and denosumab ³