Mishaela Rubin, MD, MS, is a professor of medicine at Columbia University Irving Medical Center.

Mishaela Rubin, MD, MS

Managing Renal Function and Serum Calcium in Hypoparathyroidism, With Mishaela Rubin, MD, MS

Published in October 2025, a new set of best practice recommendations for the treatment of 

 has updated the existing 2022 international guidelines by incorporating therapeutics from the past 3 years, including the recently approved molecule palopegteriparatide.

HypoPT is a metabolic disorder occurring as a result of hypocalcemia and hyperphosphatemia, which are in turn caused by either a failure of the parathyroid glands to secrete sufficient amounts of active PTH or an inability of PTH to induce a biological response in target tissues. 75% of all cases are caused by surgery, but nonsurgical causes can include autoimmune, genetic variants, metastatic, and radiation.

These updated best practice statements were drafted by a team of international HypoPT experts and resulted from an initiative launched by the Canadian Society of Endocrinology and Metabolism (CSEM) in partnership with several other international endocrine societies. The document aims to provide a practical framework to guide PTH replacement therapy usage with palopegteriparatide in chronic HypoPT.

 editorial team sat down with Mishaela Rubin, MD, MS, professor of medicine at Columbia University Irving Medical Center and a contributing author to the new recommendations, to discuss her thoughts on optimal HypoPT care, including postsurgical risk assessment, genetic evaluation, and dose titration of parathyroid hormone (PTH) therapies.

“I think that clinicians who aren’t sensitized or aren’t aware of hypoparathyroidism might not think about lab results that might be suggestive or what they might mean,” Rubin told 

. “I oftentimes see patients who’ve had symptoms and been seen by different doctors, but nobody made the diagnosis.”

The recommendations open by covering challenges presented by HypoPT, both in diagnosis and treatment. In addition to the disease’s own effects, conventional therapies, such as oral calcium supplements, can potentially increase serum phosphorus, hypercalciuria, and hypercalcemia, and could contribute to renal function declines.

The document goes on to establish optimal uptake and dose titration for PTH and PTH analogues, emphasizing its proven efficacy in reducing urine calcium excretion and maintaining eucalcemia. Ultimately, however, the recommendations shift to palopegteriparatide, a recently approved treatment consisting of PTH (1-34) linked to a polyethylene glycol moiety. With a half-life of roughly 60 hours and providing a sustained release of active PTH, palopegteriparatide allowed patients in multiple phase 2 and 3 trials to achieve total independence from conventional therapy.

The guidelines then turn to emerging therapies, such as eneboparatide, which is a long-acting PTH/PTHrP analog with evidence for lowering urine calcium, normalizing bone remodeling, and achieving eucalcemia. Eneboparatide has received fast track designation from the US Food and Drug Administration (FDA) and is currently under investigation in phase 3 clinical trials.

Ultimately, the guideline encourages close monitoring of serum calcium and renal function, outlining the risks and benefits of each potential therapy and highlighting potential upcoming treatments. The document also emphasizes that updates are expected in 5 years, provided that further long-term data is made available.

“The most important medical complication, I would say, is renal,” Rubin said. “Patients should have some type of renal imaging, at least at baseline, whether that’s a renal ultrasound or a CT scan, to look for nephrocalcinosis and nephrolithiasis. We worry about their hypocalcemic symptoms, about their struggles with neurocognitive function, but I think that careful renal screening sometimes falls under the radar.”

Editor’s Note: Rubin reports disclosures with Amgen, Ascendis, Radius, and NPS Pharmaceutical/Shire.

Khan AA, Ali DS, Bilezikian JP, et al. Best practice recommendations for the diagnosis and management of hypoparathyroidism. Metabolism. 2025;171:156335. 

Hakami Y, Khan A. Hypoparathyroidism. Front Horm Res. 2019;51:109-126. 

https://pubmed.ncbi.nlm.nih.gov/30641528/

Videos

Rubin discusses the recently released best practice recommendations for HypoPT treatment, explaining how clinicians can help turn this dangerous disease around.

Palopegteriparatide Allows for PTH Tapering in Hypoparathyroidism, With Mishaela Rubin, MD, MS

Palopegteriparatide’s efficacy and safety profile for patients with 

 has been reaffirmed by a recent real-world analysis of patients enrolled in a US expanded access program, which also provided insight into outcomes of different treatment transition processes.

The expanded access program was undertaken by Ascendis Pharma for the purpose of investigating patients who had previously received PTH treatment but were ineligible for an ongoing clinical trial of palopegteriparatide.

“Overall, the results were very similar to what was seen in the more rigorous clinical trials, namely that patients were able to come off of their standard of care requirements while maintaining a normal serum calcium level,” Mishaela Rubin, MD, MS, professor of medicine at Columbia University Irving Medical Center and investigator on the expanded access program, said in an interview with 

. “I think it was reassuring, taking our experience out of the very regimented scope of the clinical trial and moving it out into a real-world population.”

For inclusion in the program, these patients were also required to have a serum albumin-adjusted calcium level ≥7.8 mg/dL and 25(OH) vitamin D in the normal range for 2 weeks prior to the first dose, as well as a body mass index (BMI) 17-40 kg/m2. Patients were excluded if they were currently enrolled in an investigational drug or device study or had severe renal impairment, increased risk for osteosarcoma, active malignancy within the last 2 years, or severe or decompensated cardiac disease within 26 weeks.

Palopegteriparatide is a prodrug of parathyroid hormone (PTH) (1-34), designed to provide active PTH within the physiological range for 24 hours daily. The PTH released from palopegteriparatide has a half-life of roughly 60 hours. Doses are given subcutaneously once daily via a prefilled pen.

During the program, patients would receive palopegteriparatide as a solution with a concentration of 0.3 mg PTH (1-34)/mL in a prefilled pen for subcutaneous injection. Initiation and titration were guided by a protocol-specified algorithm guided by serum calcium levels. Serum calcium was measured locally 7-14 days after initiating or titrating palopegteriparatide, at a minimum of every 2 months after the maintenance dose was reached.

Ultimately, 135 patients enrolled in the extended access program and received ≥1 dose of palopegteriparatide – of these, 123 consented to share their data and were included in the final analysis. At the data cut for the analysis, 96.7% of patients remained on palopegteriparatide treatment. Most patients were diagnosed with postsurgical hypoparathyroidism (82.1%). Investigators noted comorbidities including anxiety (13.8%), thyroid cancer not otherwise specified (10.6%), papillary thyroid cancer (9.8%), nephrolithiasis (8.9%), and 

Of the total enrolled patients, 62 (50.4%) were classified as direct switch, which was defined as having stopped short-lived PTH therapy ≤1 day prior to palopegteriparatide initiation, including overlapping therapy. Another 61 patients were nondirect switch, defined as stopping short-lived PTH therapy ≥2 days before initiation.

Among the direct switch patients, 80.4% (n = 41) achieved independence from conventional therapy by month 3, and all patients achieved independence by month 12. 75% of the nondirect switch patients (n = 36) achieved independence from conventional therapy by month 3, and 66.7% of the remainder achieved independence by month 12. Mean serum calcium was within the reference range at each time point, with a mean of 8.8 mg/dL (standard deviation [SD], 0.6) at month 12. Direct switch patients maintained normocalcemia over 12 months of treatment with a mean of 9.1 mg/dL (SD, 0.7) at month 3 and 9.1 mg/dL (SD, 0.6) at month 12. For nondirect switch patients, normocalcemia was maintained over 12 months with a mean of 9.3 mg/dL (SD, 0.9) at month 3 and 8.3 mg/dL (SD, 0.3) at month 12.

Despite these positive results, however, data is still needed regarding switching hypoparathyroidism therapies. Little data exists regarding the process by which clinicians should transition from one given PTH to another.

“It’s important to ask, is there a protocol for how to stop one PTH and start the other? Should it be the same day? Should it even be overlapping by a day?” Rubin said. “We also want data about what happens when patients might need to stop palopegteriparatide. I think having more information about changes like that would be important.”

Graham T, Shoback DM, Abbott L, et al. Early U.S. Real-World Treatment Patterns and Outcomes in Palopegteriparatide Treatment for Patients With Hypoparathyroidism. 

Ascendis Pharma Bone Diseases A/S. Expanded Access Program of Palopegteriparatide in Patients with Hypoparathyroidism. ClinicalTrials.gov Identifier: NCT05654701. Updated June 27, 2025. Accessed January 8, 2026. 

https://www.clinicaltrials.gov/study/NCT05654701

Rubin discusses an analysis of Ascendis’s program for patients who had received PTH treatment but weren’t eligible for clinical trials of palopegteriparatide.

Mishaela Rubin, MD, MS

Articles