NOT FOR HUMAN CONSUMPTION

Teriparatide is a recombinant human parathyroid hormone fragment comprising the N-terminal 34 amino acids of endogenous PTH (PTH 1–34). It is administered as a once-daily subcutaneous injection and is the prototypical anabolic (bone-forming) osteoporosis therapy.

Regulatory status
Teriparatide is an approved medicine in major markets (e.g., Forteo in the US; Forsteo in Europe), with multiple approved generics/biosimilars depending on jurisdiction.

2) Clinical indications (label-based)

From US and EU labeling, teriparatide is used for osteoporosis in adults at high risk of fracture, including:

• Postmenopausal women with osteoporosis at high risk for fracture (reduces vertebral and non-vertebral fractures).

• Men with primary or hypogonadal osteoporosis at high risk for fracture (increases bone mass).

• Men and women with glucocorticoid-induced osteoporosis at high risk for fracture.

(Exact wording varies slightly by product/region, but the “high fracture risk / failed or intolerant to other therapy” framing is consistent across labels.)

3) Molecular mechanism of action

3.1 Receptor pharmacodynamics

Teriparatide is an agonist of the PTH1 receptor (PTH1R) (a class B GPCR) expressed on osteoblast lineage cells (and renal tubular cells). Its biology is defined by a key principle:

Intermittent PTH1R stimulation → net bone formation
Continuous PTH excess → net bone resorption

This “intermittency effect” is the central mechanistic reason daily teriparatide is anabolic.

3.2 Cellular and tissue-level effects (how bone mass rises)

Intermittent teriparatide increases bone formation largely by increasing the number and activity of osteoblasts, via:

• activation of existing osteoblasts,

• promotion of osteoblast differentiation from progenitors,

• reduced osteoblast apoptosis (context-dependent),

• stimulation of remodeling and modeling-based formation.

A characteristic biomarker pattern is the “anabolic window”: bone formation markers rise first, followed later by resorption markers.

3.3 Downstream signaling (high-level)

PTH1R signaling involves cAMP/PKA and related pathways in bone cells, which shifts transcriptional programs toward osteoblast function and alters osteoblast–osteoclast coupling (e.g., via RANKL/OPG dynamics), producing net anabolic effects when dosed intermittently.

4) Pharmacokinetics and administration

Route: Subcutaneous injection, 20 μg once daily is the canonical dose for originator products.
As a peptide hormone fragment, teriparatide has rapid systemic clearance relative to monoclonal antibodies and acts through pulsatile daily exposure, consistent with its anabolic mechanism (the “intermittent vs continuous” paradigm).

5) Clinical efficacy (what it reliably does)

5.1 Fracture risk and BMD

In postmenopausal osteoporosis, teriparatide reduces vertebral and non-vertebral fractures and increases BMD (especially spine).

5.2 Glucocorticoid-induced osteoporosis

Teriparatide is used in adults with osteoporosis associated with sustained systemic glucocorticoids at high fracture risk and increases bone mass; it is often considered when fracture risk is very high or antiresorptives are insufficient/tolerability-limited.

5.3 Practical place in therapy

Guidelines vary, but teriparatide is classically positioned for very high fracture risk (multiple fractures, very low T-score, or failure/intolerance of other therapies), and commonly followed by an antiresorptive “consolidation” therapyto maintain gains (because anabolic gains can regress after stopping without follow-on treatment). (This sequencing approach is widely taught in osteoporosis practice; check your local guideline for exact phrasing.)

6) Safety and tolerability (label-informed, mechanism-informed)

6.1 Common adverse effects

Typical adverse effects include:

• nausea, headache, dizziness

• orthostatic hypotension (particularly early after injection)

• leg cramps

• hypercalcemia (usually mild/transient; monitor if risk factors)

6.2 Osteosarcoma signal: what changed and what remains

• The US boxed warning about osteosarcoma was removed (label change noted in 2020), reflecting postmarketing surveillance and risk evaluation.

• However, labeling still includes discussion/precautionary language around osteosarcoma risk and recommends avoiding use in patients with conditions that increase baseline osteosarcoma risk (e.g., Paget disease of bone, unexplained elevated alkaline phosphatase, prior skeletal radiation, bone metastases).

6.3 Use duration

Historically, teriparatide had a 24-month lifetime limit in many settings; labeling language evolved after the boxed warning removal, but long-term use beyond 2 years remains a specialist decision balancing risk/benefit and the limited long-duration dataset.

7) Regulatory landscape

• US: Forteo label updated; boxed warning removed; teriparatide injections (originator and generics) have current prescribing information available.

• EU: Forsteo remains an authorized product with an EMA EPAR and product information.

8) Comparative positioning (quick matrix)

9) Future directions and clinical science questions

High-value ongoing questions in the field are less about “does it work” and more about optimization:

• Sequence strategies (anabolic first vs antiresorptive first in very high-risk patients)

• Personalized duration and monitoring strategies after label changes

• Combination/transition protocols to preserve BMD and reduce rebound risk

• Better fracture-risk stratification to target anabolic therapy cost-effectively

Selected references (most load-bearing)

• Current US Forteo prescribing information (2024 label):

• EMA Forsteo product information (SmPC):

• “Intermittent vs continuous PTH” principle and clinical pharmacology summary:

• Osteosarcoma warning history and evidence review:

• Biomarker pattern (formation then resorption)