Teriparatide

Teriparatide is the first and best-known anabolic (bone-building) drug for osteoporosis. Almost every other osteoporosis treatment is anti-resorptive - it slows the cells that break bone down. Teriparatide does the opposite: it switches on the cells that build bone up, so it can rebuild a depleted skeleton rather than simply preserving what remains.

Chemically it is recombinant human parathyroid hormone (PTH) 1-34 - the first 34 amino acids of natural PTH, which is the part that carries the hormone's activity. It is given as a once-daily subcutaneous injection for a limited period.

For the exam, three threads recur throughout this topic: how an anabolic drug differs from the anti-resorptives you already know, the intermittent-versus-continuous PTH paradox that explains why it works, and how it is used in practice - who gets it, the evidence behind it, the 24-month limit, and the essential follow-on with an anti-resorptive.

Parathyroid hormone is the body's main regulator of calcium. Its effect on the skeleton depends entirely on how the bone is exposed to it, and this is the single most important concept in the topic.

View larger

What happens at the cell level with intermittent dosing:

• A daily injection produces a short spike of PTH that quickly clears.
• This brief pulse acts on osteoblasts (the bone-forming cells) through the PTH/PTHrP receptor, increasing their number and activity and reducing their programmed death.
• The result is a burst of new bone formation that outpaces resorption, so bone mass rises and trabecular architecture is rebuilt - genuinely new bone, not just preserved old bone.
• Because the level falls again between doses, the prolonged signal that would otherwise switch on osteoclasts (through RANKL on osteoblasts) is avoided.

By contrast, when PTH stays high all the time - as in primary hyperparathyroidism - the same receptor signalling sustains RANKL expression, osteoclasts dominate, and bone is steadily resorbed. Same hormone, opposite outcome, decided by the timing of exposure.

This anabolic action also explains the "anabolic window": bone formation rises immediately, while resorption catches up only later, so the early months of treatment give the greatest net gain. Starting with teriparatide before an anti-resorptive (rather than after) tends to make the most of that window.

A closely related anabolic agent, abaloparatide, is a PTH-related protein analogue with a similar profile. Romosozumab (an anti-sclerostin antibody) is another bone-building option but works by a different mechanism. For the exam, teriparatide is the prototype anabolic drug and the one to discuss by default.

Teriparatide is reserved for severe or high-risk osteoporosis rather than first-line use, because of its cost, the daily injection, and the duration limit.

Teriparatide turns up across the exam and orthopaedic practice precisely because it is the odd one out. In basic-science vivas it is the go-to example of an anabolic drug and the home of the intermittent-versus-continuous PTH paradox - a favourite way to test whether a candidate truly understands bone biology rather than memorising drug names. In the fracture and metabolic-bone clinic it is the escalation option for severe osteoporosis and treatment failure, and it forces the candidate to discuss drug sequencing (build then preserve). In trauma, it appears in discussions of atypical femoral fractures and difficult or fragile fracture healing, where its bone-building action is attractive. Knowing what it is, why intermittent dosing matters, who to give it to, and what to do afterwards is the practical core examiners probe.

Common, usually minor side effects include nausea, headache, dizziness, leg cramps, and a transient small rise in serum calcium after each dose. Check that the patient is not hypercalcaemic before starting.

• Major osteoporosis guidelines (for example the Endocrine Society, AACE, NOGG in the UK, and bone-health initiatives endorsed by AAOS/AOA) position teriparatide as a treatment for severe or very high fracture-risk osteoporosis and for patients who fracture or lose bone despite an anti-resorptive, rather than as a first-line agent.
• Anabolic-first sequencing is increasingly endorsed for the highest-risk patients (those with recent or multiple vertebral fractures), reflecting head-to-head trial evidence that anabolic therapy reduces vertebral fractures more than oral bisphosphonates in this group.
• Guidance consistently stresses the mandatory follow-on anti-resorptive after stopping teriparatide to preserve bone gained, and the 24-month lifetime limit.
• Global practice variation is driven mainly by cost and access - the daily injection and price mean teriparatide is reserved for selected high-risk patients in most health systems, while the underlying principles (build then preserve, reserve for severe disease) are consistent worldwide.