Parathyroid Substance
Also known as: PTH, parathyroid substance, rhPTH(1–84), PTH(1–34), teriparatide, Parathyroid hormone
Overview
Parathyroid hormone (PTH) is a polypeptide hormone naturally secreted by the parathyroid glands, playing a crucial role in regulating calcium and phosphate metabolism. While an endogenous hormone, 'Parathyroid Substance' in a therapeutic context refers to recombinant forms of PTH, such as rhPTH(1–84) and PTH(1–34) (teriparatide), which are not sourced naturally as supplements but produced for clinical use. Therapeutically, PTH is primarily used to manage chronic hypoparathyroidism, a condition characterized by deficient PTH secretion, and osteoporosis. Its mechanism involves increasing serum calcium by stimulating bone resorption, enhancing renal calcium reabsorption, and activating vitamin D metabolism. PTH is a well-studied agent in clinical endocrinology, supported by high-quality evidence from numerous randomized controlled trials and meta-analyses, confirming its efficacy and safety for specific endocrine disorders. It is administered via injection and is considered a prescription biologic agent rather than a conventional dietary supplement.
Benefits
Parathyroid hormone (PTH) therapy offers significant benefits, particularly for patients with chronic hypoparathyroidism and osteoporosis. In chronic hypoparathyroidism, rhPTH(1–84) therapy significantly reduces the need for active vitamin D and calcium supplementation, with a relative risk (RR) of 6.5 (95% CI 2.5–16.4) for achieving a ≥50% dose reduction compared to conventional therapy. This reduction in supplementation requirements is clinically meaningful, improving patient management. PTH therapy also modestly improves physical health-related quality of life, showing a mean difference of 3.4 points on a standardized scale (95% CI 1.5–5.3). While PTH therapy may increase the risk of hypercalcemia (RR = 2.4, 95% CI 1.2–5.04), the certainty of this evidence is low. Beyond direct PTH therapy, vitamin D2 supplementation has been shown to reduce endogenous PTH levels by approximately 12.77 pg/mL (95% CI −20.03 to −5.51), improving calcium homeostasis in populations with vitamin D insufficiency. The effects of PTH therapy are typically observed over 1 to 36 months in clinical trials, while vitamin D2's impact on PTH can be seen within weeks to months.
How it works
Parathyroid hormone (PTH) exerts its effects primarily by binding to PTH1 receptors located on bone cells (osteoblasts) and renal tubular cells. In bone, PTH stimulates osteoclast-mediated bone resorption, leading to the release of calcium into the bloodstream. In the kidneys, it enhances calcium reabsorption, reducing its excretion. Additionally, PTH activates the enzyme 1-alpha hydroxylase in the kidneys, which is crucial for converting inactive vitamin D into its active form, calcitriol. Calcitriol, in turn, further enhances intestinal calcium absorption. This multi-faceted action allows PTH to effectively regulate calcium and phosphate metabolism and modulate bone remodeling. Recombinant PTH is administered via injection, as it has negligible oral bioavailability.
Side effects
Parathyroid hormone (PTH) therapy is generally considered safe when administered under medical supervision, but it requires careful monitoring due to potential side effects. The most common adverse effects, occurring in over 5% of patients, include injection site reactions and mild hypercalcemia. Less common side effects, affecting 1-5% of users, may include nausea and headache. A rare but notable concern, observed in animal studies, is an increased risk of osteosarcoma; however, this risk has not been confirmed in humans at therapeutic doses. Patients should be cautious about drug interactions, particularly with calcium supplements and vitamin D analogs, as concurrent use can exacerbate the risk of hypercalcemia. Contraindications for PTH therapy include pre-existing hypercalcemia, bone malignancies, or unexplained elevations of alkaline phosphatase. Special considerations apply to specific populations: its use in pregnancy and pediatric patients is limited and requires specialized medical oversight due to insufficient safety data in these groups. Regular monitoring of serum calcium and phosphate levels is essential to manage potential risks effectively.
Dosage
For recombinant human parathyroid hormone (rhPTH(1–84)), the typical starting dose is 50–100 mcg administered daily via subcutaneous injection. The optimal dosage range is highly individualized and must be adjusted based on the patient's serum calcium and vitamin D levels, as well as their clinical response. There is no firmly established maximum safe dose; clinical guidelines emphasize using the lowest effective dose to achieve therapeutic goals while minimizing risks. PTH is administered as a daily injection, and the timing relative to meals is not considered critical. It is crucial to note that PTH is only available in injectable forms and is not orally bioavailable. Adequate intake of calcium and vitamin D is essential as cofactors to support the therapeutic effects of PTH and maintain overall mineral balance.
FAQs
Is parathyroid substance available as an oral supplement?
No, parathyroid hormone (PTH) is a protein hormone that is only available as a prescription injectable medication, as it would be digested if taken orally.
Can PTH therapy replace calcium and vitamin D supplements?
PTH therapy can significantly reduce the need for calcium and vitamin D supplements in patients with hypoparathyroidism, but it may not always eliminate the need entirely. Supplementation is often still required, albeit at lower doses.
How quickly does PTH therapy improve symptoms?
Improvements in biochemical parameters, such as calcium levels, typically occur within weeks of starting PTH therapy. However, improvements in quality of life and other clinical symptoms may take several months to become noticeable.
Is vitamin D2 effective in lowering PTH?
Yes, vitamin D2 supplementation has been shown to significantly lower endogenous PTH levels, particularly in individuals who are deficient in vitamin D, thereby contributing to improved calcium homeostasis.
Research Sources
- https://boneresearch.ca/wp-content/uploads/2022/11/JBMR_PTH-SR.pdf – This systematic review and meta-analysis of 7 RCTs (386 patients) found that PTH therapy for chronic hypoparathyroidism significantly reduces the need for calcium and vitamin D supplementation (RR=6.5) and improves quality of life. It also noted a potential, though low-certainty, increase in hypercalcemia risk. The study highlights the clinical benefits of PTH while acknowledging limitations like small sample sizes and short durations.
- https://academic.oup.com/nutritionreviews/advance-article/doi/10.1093/nutrit/nuaf102/8182699 – This systematic review and meta-analysis of 26 RCTs demonstrated that vitamin D2 supplementation effectively reduces serum PTH levels by an average of 12.77 pg/mL and modestly increases calcium levels. Despite high heterogeneity across studies, the findings consistently support vitamin D2's role in improving calcium homeostasis in vitamin D insufficient populations.
- https://pubmed.ncbi.nlm.nih.gov/26337807/ – This systematic review and meta-analysis of RCTs concluded that the response of PTH levels to vitamin D supplementation is dependent on baseline vitamin D status and the specific dose administered. It underscores the importance of individualized approaches to vitamin D supplementation for optimal PTH regulation.
