Parathyroid Hormone Analogues

Parathyroid hormone analogues give daily pulses of PTH receptor agonist to build bone in severe osteoporosis, and in some regions replace missing hormone in hypoparathyroidism. They are the anabolic agents of osteoporosis therapy.

Mechanism. Intermittent PTH1 receptor activation stimulates osteoblast formation and survival, so that bone formation exceeds resorption. Continuous exposure (for example in hyperparathyroidism) causes net bone loss.

Pharmacokinetics. Subcutaneous injection, rapid absorption, half-life about 1 hour, peak calcium rise at 4 to 6 hours.

Teriparatide. PTH 1-34, 20 micrograms subcutaneously daily for up to 24 months.

Abaloparatide. PTH-related protein analogue, 80 micrograms subcutaneously daily for up to 24 months, available in limited regions.

Parathyroid hormone 1-84. 50 micrograms subcutaneously daily, adjusted by 25 micrograms every 4 weeks to a maximum of 100 micrograms, for hypoparathyroidism where available.

Long acting prodrug (palopegteriparatide). Daily for hypoparathyroidism in some regions; confirm availability and dosing locally.

Versus antiresorptives. Greater vertebral fracture reduction and benefit in glucocorticoid-induced osteoporosis, but expensive, injectable and limited in duration.

• Severe osteoporosis: vertebral fractures, very low T-score, fractures on antiresorptive therapy, and glucocorticoid-induced osteoporosis.
• Sequence: follow with an antiresorptive (bisphosphonate or denosumab) to keep the gain. Prior alendronate blunts the early response; prior denosumab can cause transient hip bone loss.
• Administration: the first doses given seated, then in the thigh or abdomen. Pens are kept at 2 to 8 degrees C and used within 28 days.
• Hypoparathyroidism: reduce calcitriol and calcium as the dose is titrated; goal serum calcium at the lower end of the normal range.

Special groups. Pregnancy: avoid. Breastfeeding: avoid. Children: avoid with open growth plates. Older adults: orthostatic dizziness at first doses. Kidney impairment: avoid at eGFR under 30 mL/min. Liver impairment: caution.

Adverse effects. Nausea, leg cramps, dizziness and postural hypotension, transient hypercalcaemia, hypercalciuria, hyperuricaemia, and injection site reactions. Osteosarcoma occurred in rats; no excess has been shown in patients, but treatment is limited to 24 months.

Contraindications. Paget disease, unexplained raised alkaline phosphatase, previous skeletal radiotherapy, skeletal malignancy or bone metastases, hypercalcaemia, primary hyperparathyroidism, open epiphyses, and prior osteosarcoma.

Interactions. Digoxin toxicity with hypercalcaemia. Thiazides add hypercalcaemia.

Monitoring. Calcium at 1 and 3 months (4 to 6 hours after a dose), alkaline phosphatase, urinary calcium if stones, and bone density at 12 and 24 months.

Referral and escalation. Persistent hypercalcaemia, bone pain with raised alkaline phosphatase, or a new fracture despite therapy.