Teriparatide 💊

Related Subjects: | Osteoporosis

💡 Teriparatide is the first approved bone anabolic therapy for severe osteoporosis. It mimics the actions of parathyroid hormone (PTH), stimulating new bone formation rather than merely slowing bone loss. 🏥 Reserved for severe or refractory osteoporosis where bisphosphonates or denosumab are unsuitable or ineffective.

🧠 About

• Recombinant form of human parathyroid hormone (PTH 1-34), the biologically active portion of endogenous PTH.
• It works by intermittently activating PTH receptors on osteoblasts, leading to increased bone formation and skeletal mass.
• Unlike bisphosphonates or denosumab, it is truly anabolic - it builds bone rather than merely preserving it.
• Shown to significantly reduce vertebral and non-vertebral fracture risk in severe osteoporosis.

⚙️ Mechanism of Action

• Continuous high PTH exposure → bone resorption; intermittent low-dose exposure → bone formation. Teriparatide exploits this physiological distinction.
• Stimulates osteoblast differentiation and activity, enhances calcium reabsorption in the kidney, and increases intestinal calcium absorption indirectly via vitamin D.
• Results in thicker trabeculae, improved microarchitecture, and increased bone mineral density (BMD).

🎯 Indications

• Severe osteoporosis in postmenopausal women or men at very high fracture risk (e.g. multiple vertebral fractures or very low BMD).
• Osteoporosis secondary to prolonged corticosteroid therapy.
• Patients intolerant of or unresponsive to bisphosphonates/denosumab.

💉 Dose and Duration

• Teriparatide 20 micrograms subcutaneously once daily, usually self-administered into the thigh or abdomen.
• Maximum duration: 24 months (lifetime limit).
• Follow-on treatment with an antiresorptive agent (e.g. bisphosphonate or denosumab) is recommended to consolidate gains in BMD after stopping therapy.

⚠️ Contraindications

• Pre-existing hypercalcaemia or hyperparathyroidism.
• Paget’s disease of bone or unexplained elevations of alkaline phosphatase.
• Skeletal malignancy or prior radiation therapy to the skeleton.
• Metabolic bone diseases other than osteoporosis.
• Children or young adults with open epiphyses.

⚠️ Cautions

• Use only under specialist supervision; avoid in severe renal impairment.
• Monitor serum calcium, vitamin D, and renal function before and during treatment.
• Orthostatic hypotension may occur after injection - advise patients to sit or lie down after administration.
• Follow treatment with a potent antiresorptive to maintain bone gains.

💥 Side Effects

• Common: Nausea, dizziness, headache, palpitations, reflux, constipation or diarrhoea.
• Metabolic: Transient hypercalcaemia (4–6 h post-dose), muscle cramps, increased sweating.
• Rare: Depression, anaemia, arthralgia, leg pain or sciatica.
• Animal studies suggested osteosarcoma risk, but this has not been demonstrated in humans at therapeutic doses.

💡 Teaching Tip

• Teriparatide demonstrates the principle of intermittent versus continuous hormone signalling - low-dose pulsatile PTH stimulates bone growth, continuous PTH causes bone loss.
• Mnemonic: “Teri BUILDS the bone” - remember it as the *builder* in contrast to bisphosphonates (the *preservers*).
• Teach that sequential therapy (Teriparatide → Bisphosphonate) is key to maximising and sustaining bone density gains.

📚 References

• BNF: Teriparatide
• NICE TA161 (updated 2023): Teriparatide for the treatment of osteoporosis
• Neer RM et al., NEJM 2001;344:1434 – 1441 - Landmark trial on PTH (1-34) reducing fracture risk.