Parathyroid Hormone (PTH)
Also known as: PTH, teriparatide, PTH 1-84, abaloparatide, natpara
Endogenous 84-amino acid peptide hormone; parathyroid gland secretory product; PTH1 receptor (PTH1R) agonist; osteoanabolic bone agent; calcium-regulating hormo
What it is
Parathyroid hormone (PTH) and its analogues are used by people with osteoporosis who need stronger bones rebuilt, not just protected. Teriparatide (PTH 1-34) and abaloparatide are daily injections that stimulate new bone formation, reducing spine and hip fractures. PTH 1-84 (Natpara) treats chronic hypoparathyroidism when calcium supplements alone are insufficient.
The scientific side
Parathyroid Hormone (PTH) is a 84-amino acid peptide secreted by the parathyroid glands in response to falling serum ionised calcium. Its physiological actions are mediated principally through the G-protein-coupled PTH type 1 receptor (PTH1R), which is expressed on osteoblasts, osteocytes, renal tubular cells, and a broad range of mesenchymal progenitors. PTH1R activation stimulates intracellular cAMP and protein kinase A signalling, initiating transcriptional programmes that drive bone anabolism when PTH is administered intermittently. The osteoanabolic mechanism of intermittent exogenous PTH is mechanistically distinct from the catabolic effects of chronic endogenous PTH elevation seen in hyperparathyroidism. Lineage-tracing and single-cell transcriptomic studies in mice (PMID 42244729) demonstrate that intermittent PTH drives osteogenesis from Ebf3-expressing CAR (CXCL12-abundant reticular) cells by two convergent pathways: cell-intrinsic suppression of lineage-enforcing transcription factors Ebf3, Ebf1, and Foxc1 that destabilises progenitor identity and primes cells for osteogenic commitment; and cell-extrinsic stimulation of osteoclastic resorption, which releases TGF-beta that recruits these primed progenitors to bone surfaces. Ablating osteoclasts or deleting Sp7 in CAR cells both abolish iPTH-induced bone gain, confirming this dual mechanism is essential. These mechanisms were conserved in human CAR cells from teriparatide-treated postmenopausal women. Genetic mouse studies show that skeletal response to intermittent PTH is highly strain- and sex-dependent, with heritability estimates for PTH-induced changes in trabecular bone volume fraction ranging from moderate to high; cortical bone response mechanisms differ by sex — males exhibit periosteal expansion while females show endosteal remodelling — mirroring clinical observations of variable and anatomic site-specific non-response (PMID 42829196). The temporal waning of osteoanabolic efficacy that occurs within 12–18 months of PTH analog treatment is attributed to receptor desensitisation at PTH1R, depletion of available bone-forming surfaces, exhaustion of osteoblast progenitors, and upregulation of endogenous Wnt antagonists such as sclerostin and DKK1 (PMID 41841800). In the kidney, PTH1R activation promotes phosphaturia and stimulates production of 1,25-dihydroxyvitamin D, thereby increasing intestinal calcium absorption and maintaining calcium homeostasis.
Class: Endogenous 84-amino acid peptide hormone; parathyroid gland secretory product; PTH1 receptor (PTH1R) agonist; osteoanabolic bone agent; calcium-regulating hormone
Administration & storage
- Administration
- Subcutaneous injection into the thigh or abdominal wall: the recommended and only approved route for teriparatide. Inject at a 90-degree angle using the pen device; rotate injection sites within the same anatomic regions. Avoid areas with visible veinsscar tissuestretch marksor areas that are bruisedtenderor hard.Subcutaneous injection for PTH 1-84 (Natpara): thigh or abdominal wall; single daily injection; dose titrated per serum calcium response.Subcutaneous injection for abaloparatide (Tymlos): periumbilical abdominal region only (as per FDA label); rotate sites; 80 mcg per dose once daily.Intramuscular injection: not routinely used for approved PTH analogue formulations; some preclinical and early phase studies used IM dosing.
- Storage
- Teriparatide pen: store in refrigerator at 2–8°C (36–46°F); do not freeze or shake; keep in the original carton to protect from light; discard 28 days after first use even if solution remains; never store with a needle attached. During travel, may be kept at room temperature below 25°C (77°F) for up to 28 days. Natpara: refrigerate at 2–8°C until first use; after first reconstitution in device, refrigerate and use within 14 days. Abaloparatide (Tymlos): refrigerate at 2–8°C; once in use, may be stored at room temperature below 25°C for up to 30 days; discard after 30 days.
- Cautions
- Osteosarcoma (historical black box warning): teriparatide originally carried an FDA black box warning for osteosarcoma based on dose-dependent tumours in long-term rat studies; this warning was removed in 2020 following pharmacoepidemiologic evidence of no elevated osteosarcoma incidence in humans (PMID 35318162); however, teriparatide remains contraindicated in patients with elevated baseline risk of osteosarcoma including prior radiation therapy to the skeleton, Paget's disease of bone with elevated alkaline phosphatase, open epiphyses (children), and prior skeletal malignancy.,Hypercalcemia: serum calcium should be monitored periodically; transient hypercalcemia may occur within hours of injection, typically resolving before the next dose; persistent or symptomatic hypercalcemia requires dose reduction or discontinuation.,Hypercalciuria and nephrolithiasis: urinary calcium excretion may increase; patients with pre-existing urolithiasis or hypercalciuria should be assessed before initiation; renal function should be monitored throughout treatment.,Orthostatic hypotension: some patients experience transient dizziness or palpitations shortly after injection, likely from a vasodilatory effect of PTH; patients should inject while sitting or lying down initially and remain seated for a few minutes after injection.,Renal impairment: use with caution in moderate to severe renal impairment (eGFR < 35 mL/min); teriparatide is contraindicated in severe renal impairment; the CKD systematic review (PMID 42825520) noted higher adverse event frequency in CKD patients.,Duration limit: lifetime maximum of 24 months for teriparatide and abaloparatide; patients who have already received a cumulative 2-year course should not receive additional teriparatide unless formal guidelines evolve.,Paediatric and adolescent use: not approved for use in children or adolescents with open epiphyses; off-label use in exceptional circumstances (e.g., OI with delayed fracture healing) requires specialist oversight and close monitoring for hypercalcemia (PMID 42484024).
Legal & regulatory status
Teriparatide (recombinant human PTH 1-34; Forteo, Eli Lilly) was first approved by the US FDA in November 2002 for treatment of postmenopausal women with osteoporosis at high fracture risk, men with primary or…
PTH and its synthetic analogues (teriparatide, abaloparatide, PTH 1-84) are listed on the WADA Prohibited List under Section S2 (Peptide Hormones, Growth Factors, Related Substances, and Mimetics) and are prohibited…
Teriparatide (Forteo) is approved by Health Canada for treatment of osteoporosis in postmenopausal women with prior vertebral fractures and for men with osteoporosis at increased risk of fractures; maximum treatment…
What it's studied for
- Postmenopausal osteoporosis — vertebral and non-vertebral fracture prevention Phase III RCT / FDA-approved indication
- Glucocorticoid-induced osteoporosis — bone density restoration Phase III RCT / FDA-approved indication
- Spinal fusion surgery optimisation — reducing proximal junctional kyphosis and pseudarthrosis Systematic review and meta-analysis (RCTs and observational studies)
- Hypoparathyroidism — PTH replacement therapy FDA-approved indication (PTH 1-84) / Clinical case series (teriparatide off-label)
- Fracture healing augmentation — delayed union and complex healing Systematic review / Case reports / Off-label use
- Chronic kidney disease-associated osteoporosis — bone mineral density improvement Systematic review of RCTs (limited evidence)
- Pregnancy and lactation-associated osteoporosis — anabolic rescue therapy Cohort study / Observational registry data
Safety signals
- Osteosarcoma (historical, black box warning removed 2020)
- Hypercalcemia — transient and persistent
- Orthostatic hypotension and dizziness shortly after injection
- Waning osteoanabolic efficacy with prolonged use (12–18 months)
- Nausea, leg cramps, and injection site reactions
- Variable skeletal response based on genetic background and sex
- Hypercalciuria and nephrolithiasis risk
All studies (7)
Frequently asked
How long can I use teriparatide (Forteo)?
Teriparatide is approved for a maximum of 24 months (2 years) over your lifetime. This limit exists because clinical trials were conducted for up to 2 years and the waning of bone-building effects within 12–18 months means longer treatment provides diminishing benefit. After completing a teriparatide course, your doctor will typically transition you to an antiresorptive medication (such as a bisphosphonate or denosumab) to preserve the bone you have gained.
Does teriparatide cause cancer or bone tumours?
Earlier versions of the teriparatide prescribing information included a black box warning about osteosarcoma (a rare bone tumour) based on high-dose rat studies. However, in 2020 the FDA removed that warning after a large study of over 300,000 teriparatide-treated patients found no increase in osteosarcoma rates compared to people with osteoporosis who did not receive teriparatide (PMID 35318162). Teriparatide remains contraindicated in people with prior radiation to the skeleton, Paget's disease, or a history of bone cancer, as these already increase osteosarcoma risk independently.
Why do I feel dizzy or lightheaded after my teriparatide injection?
A small number of people experience transient dizziness, palpitations, or lightheadedness within the first few hours after injection — likely because PTH briefly dilates blood vessels. This is usually mild and self-limiting. Injecting while sitting down and remaining seated for a few minutes after administration reduces this risk. If symptoms are severe or do not resolve, contact your prescriber.
What is the difference between teriparatide, abaloparatide, and PTH 1-84 (Natpara)?
All three are forms of parathyroid hormone acting at the PTH1 receptor, but they differ in structure and indication. Teriparatide (Forteo) is the N-terminal 34 amino acids of full-length PTH and is FDA-approved for osteoporosis in postmenopausal women, men, and glucocorticoid-treated patients. Abaloparatide (Tymlos) is derived from PTH-related peptide (PTHrP) and is approved for postmenopausal osteoporosis; it may produce slightly different bone formation vs. resorption kinetics. PTH 1-84 (Natpara) is the full 84-amino acid hormone, approved as a replacement therapy for hypoparathyroidism rather than for osteoporosis; it is currently unavailable in the US due to a pen device recall.
Do I need to refrigerate my teriparatide pen?
Yes. The teriparatide pen must be stored in the refrigerator at 2–8°C (36–46°F) when not in use and should never be frozen or shaken. Keep it in its original carton to protect from light. Once opened, discard after 28 days even if solution remains. For short trips, the pen can be kept at room temperature below 25°C (77°F) for up to 28 days.