Teriparatide Nasal Spray

Hypogonadal osteoporosis results from low sex hormone levels and is commonly seen in young patients and children. Conventional injectable therapy is invasive and cumbersome, leading to poor adherence. Standard treatment combines sex hormone replacement with anti-osteoporotic agents.
The product is non-invasive and simple to use, making it more acceptable to young patients and children. It effectively improves bone mineral density and slows bone loss, with enhanced efficacy when combined with sex hormone replacement therapy.

Notably, the safety and efficacy in children and adolescents under 18 years of age have not been fully established, and use requires medical supervision.

Fracture healing is influenced by multiple factors. Osteoporotic and complex fractures are prone to complications such as delayed union. Parathyroid hormone (1-34), human (BOVINE), BOVINE stimulates osteoblast activity, boost callus formation, accelerates fracture repair, strengthens osseous , and reduces complications.
It is convenient for self-administration by postoperative patients and is suitable for long-term rehabilitation. Early postoperative use enhances callus formation, accelerates healing, and lowers the risk of non-union and refracture, especially in osteoporotic fractures. It demonstrates favorable safety and better tolerability than conventional medications.

At present, the product is still in the ongoing stage of clinical development and systematic formulation optimization.

Although it has demonstrated remarkable therapeutic potential in the intervention and treatment of multiple metabolic bone diseases, further large-scale clinical trials are still required to fully validate and refine its pharmacokinetic characteristics, overall safety profile, as well as explore and expand its clinical indications.

Current research priorities mainly focus on optimizing administration dosing regimens, further improving long-term medication safety, and broadening its scope of clinical applications, so as to lay a solid foundation for subsequent clinical translation, rational medication guidance and large-scale popularization.

01.Pharmacokinetic Studies:
Pharmacokinetic evaluation is a core component of teriparatide nasal spray development. Its primary objectives are to define key parameters including bioavailability, absorption rate, and half-life, providing scientific evidence for dosage design and administration frequency.

Due to marked differences in absorption characteristics between nasal mucosa and subcutaneous tissue, the pharmacokinetic profile of the intranasal aerosol differs substantially from injectable formulations and requires systematic clinical characterization.

Preclinical and clinical data indicate rapid absorption following nasal administration, with the drug quickly entering systemic circulation via mucosal vessels.

However, bioavailability is significantly lower than that of subcutaneous injection:In healthy human volunteers, mean peak plasma concentration (Cmax) of the intranasal aerosol  is only 5 pg/mL, compared with 253 pg/mL for the injectable form, with relative bioavailability ≤1%.

In sheep models, relative bioavailability is 1.4% for liquid intranasal aerosol and 1.0% for dry powder intranasal aerosol , whereas absolute bioavailability of subcutaneous injection reaches 77% (range 55%–108%), consistent with human clinical data (up to 95%).

Additionally, the 50% clearance time of the drug from the nasal cavity is 17.8 minutes (range 10.9–74.3 minutes), reflecting rapid elimination that shortens the duration of action.

Current development priorities include:Characterizing pharmacokinetic variability across age, sex, and hepatic/renal function via multi-dose, multi-population trials to support individualized dosing, maximizing efficacy while minimizing adverse reactions.

Change the information from this literature:PubMed, Nasal Administration and Plasma Pharmacokinetics of Parathyroid Hormone Peptide PTH 1–34 for the Treatment of bone rarefaction.

02.Safety Assessment:

Long-term use of Parathyroid hormone (1-34), human (BOVINE) carries potential safety risks, most notably hypercalcemia and osteosarcoma. As a novel delivery system, the safety profile of teriparatide nasal spray requires further long-term clinical trials to establish its benefit–risk ratio for clinical practice.
Hypercalcemia is one of the most common adverse reactions, caused by excessive stimulation of parathyroid hormone receptors leading to elevated serum calcium. Clinical data for injectable Parathyroid hormone (1-34), human (BOVINE) show transient mild hypercalcemia in normocalcemic patients, peaking at 4–6 hours and returning to baseline within 16–24 hours.

Routine calcium monitoring is generally unnecessary, but symptoms such as nausea, vomiting, and polyuria should be monitored. Due to lower bioavailability, the intranasal aerosol may carry a lower hypercalcemia risk than injections. Nevertheless, long-term trials are required to define incidence, severity, and management across dose levels, with special safety evaluation in patients with hepatic/renal impairment or a history of hypercalcemia.
Osteosarcoma risk is a major safety concern in Parathyroid hormone (1-34), human (BOVINE) development. Early preclinical studies in rats showed increased osteosarcoma incidence with long-term administration, leading to initial boxed warnings (some of which have since been removed).

However, clinical trials and post-marketing surveillance (up to 15 years) show no increased osteosarcoma risk in humans. Reported cases are rare and largely associated with confounding factors such as prior radiotherapy or underlying osseous disease. Despite this, long-term osteosarcoma risk with the product remains to be confirmed, especially in long-term users, children, and adolescents. Strict contraindications (e.g., exclusion of patients with bone malignancies or prior radiotherapy) will be established to ensure risk control.
Local safety of the nasal formulation also requires careful evaluation, including the incidence of nasal mucosal irritation, rhinitis, and epistaxis. Formulation optimization will aim to reduce local irritation and improve patient tolerability.

Serum calcium levels should be monitored regularly during treatment, especially at the initial stage (first 3 months) and after dose adjustments. Fasting serum calcium is recommended to be measured every 1–3 months. If symptoms associated with hypercalcemia occur (e.g., nausea, vomiting, constipation, thirst, polyuria, fatigue, etc.), the drug should be discontinued immediately, medical attention sought promptly, and the treatment regimen adjusted accordingly.

Long-term use may increase urinary calcium levels and raise the risk of urinary tract stones. Regular monitoring of urinary calcium excretion is recommended.

If urinary calcium remains persistently elevated, the dose should be reduced or treatment discontinued, and water intake increased to boost urinary calcium excretion.

For patients at high risk of hepatic or renal impairment, hepatic and renal function should be monitored regularly.

If abnormal liver or kidney function parameters are detected, the drug should be stopped immediately and medical treatment sought.