Chronic hypoparathyroidism and treatment with teriparatide

Abstract

Purpose Chronic hypoparathyroidism is usually treated with calcium and active vitamin D metabolites or analogs, despite the fact that their chronic use can lead to long-term complications. The use of hormone replacement therapy with PTH peptides [teriparatide and rhPTH (1–84)] has therefore been proposed. The main purpose of this study was to investigate the efficacy of teriparatide dose at 20 µg once or twice daily, in order to maintain normocalcemia reducing standard treatment, in adult patients with chronic hypoparathyroidism not well controlled with conventional treatment. Methods The study was a Phase III, open-label, non-comparative, clinical investigation (study period: 3 months), at a tertiary care clinical research center. Thirty patients with chronic hypoparathyroidism were screened, and 12 started teriparatide. After the optimization phase (0–4 weeks), calcium and calcitriol supplements were progressively reduced, while teriparatide 20 µg once daily was administered (5–7 weeks), and then could be titrated up to 20 µg twice daily (7–17 weeks). The main outcome measures included serum and urinary biochemical exams and Rand 36-Item Short Form Health Survey. Results This study showed that teriparatide 20 µg once daily was insufficient to discontinue calcium and calcitriol supplements to maintain normal serum calcium concentrations. Conversely, for more than half of patients treated with teriparatide 20 µg twice daily, calcium and calcitriol administration was avoidable, but in some cases at the expense of serum calcium and phosphate oscillations. Conclusions Since intervention trials evaluating the efficacy and safety of teriparatide in hypoparathyroid patients are not yet available, the routine use of this molecule poses some doubts.

Multicenter Retro-Prospective Observational Study on Chronic Hypoparathyroidism and rhPTH (1-84) Treatment

“…Teriparatide was initially approved with a limit of two years period treatment, then extended to three years and currently with no time limit [11]. Recently, an Italian prospective open-label investigation, conducted on 42 adult patients with postsurgical HypoPT treated with teriparatide 40 µg/daily (20 µg/twice daily) for 24 months, confirmed Winer's results [12][13][14]. However, no clinical trials for registration on teriparatide treatment have been conducted in patients with HypoPT, and no efficacy and safety data are available, especially considering the prolonged use of doses greater than 20 µg daily in young subjects and the potential risk of osteosarcoma [14].…”

“…Patients with HypoPT are usually treated with standard therapy; however, in some cases, pharmacological management can become difficult and challenging even for expert endocrinologists [3,4,18,24]. Conventional treatment, especially in case of need for high doses of calcium and calcitriol supplements, may cause long-term complications such as hypercalciuria, renal stones, nephrocalcinosis, other ectopic calcifications, and impaired renal function [2][3][4][5]14,17,18,[26][27][28]. Moreover, compliance with standard therapy is often poor and this treatment is not able to improve quality of life usually impaired in these patients [29][30][31][32].…”

“…In our cohort of patients, the main indications for switching to hormone replacement therapy were: inadequate control of serum calcium level despite conventional treatment, kidney stones, and/or gastrointestinal intolerance to supplementation calcium/malabsorption [3,4,18]. In more than half of the cases, the patients had already been treated with teriparatide (average dosage: 20 μg twice/day), however this therapy has an important limitation for this chronic pathology: the absence of therapeutic efficacy for dosages equal to 20 μg/day, the only dosage for which safety data are available from randomized and controlled studies in osteoporotic patients [4,[12][13][14]. Furthermore, even at dosages above 20 mcg/day, therapeutic efficacy in biochemical and clinical terms is not always achieved as described in our patients.…”

Hypoparathyroidism: State of the Art on Cell and Tissue Therapies

“…Currently, in selected cases of patients not responding to conventional therapy, daily injections of PTH peptides may be prescribed, in order to balance the low levels of calcium in the blood [ 6 , 14 ].…”

Differentiation of human umbilical cord mesenchymal stem cells into parathyroid cells by editing the PTH gene with the CRISPR/Cas9 system

“…Due to the low immunogenicity, unlimited proliferation and multi-directional differentiation potentials, stem cells enable the repair and regeneration of various tissues and organs [16][17][18], but the traditional induction method of stem cells has some disadvantages: such as the less harvested target cells and low purity. In addition, the long-term survival of transplanted stem cells and stable PTH secretion for maintaining constant physiological blood calcium level remain to be confirmed.…”