ECE2022 Poster Presentations Calcium and Bone (68 abstracts)
Skeletal consequences of long-term replacement therapy with human recombinant PTH(1-34) in chronic hypoparathyroidism
Rebecca Fischler 1,2 , Anne-Lise Lecoq 3 , Karine Briot 4 , Severine Trabado 5 , Florent Besson 6 , Jason Bouziotis 7 , Cecile Goujard 8 , Sylvie Salenave 1 , Sophie Leboulleux 9 , Emma Carreira 1 , Christine Chabrolle 1 , Corvilain Bernard 2 , Philippe Chanson 1,10 , Agnès Linglart 11 , Gilles Grimon 6 & Peter Kamenicky 1,10
1Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre, Service d’Endocrinologie et des Maladies de la Reproduction, Centre de Référence des Maladies Rares du Métabolisme du Calcium et du Phosphate, Le Kremlin-Bicêtre, France; 2Hôpital Erasme, Service d’Endocrinologie, Bruxelles, Belgium; 3Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre, Centre de recherche clinique, Le Kremlin-Bicêtre, France; 4Assistance Publique-Hôpitaux de Paris, Hôpital Cochin, Service de Rhumatologie, Centre de Référence des Maladies Rares du Métabolisme du Calcium et du Phosphate, Paris, France; 5Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre, Service de Génétique Moléculaire, Hormonologie et Pharmacogénétique, Le Kremlin-Bicêtre, France; 6Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre, Service de Médecine Nucléaire, Le Kremlin-Bicêtre, France; 7Hôpital Erasme, Service de la Recherche Biomédicale, Bruxelles, Belgium; 8Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre, Service de Médecine Interne, Le Kremlin-Bicêtre, France; 9Gustave Roussy, Département de Médecine Nucléaire et de Cancérologie Endocrinienne, Villejuif, France; 10Université Paris-Saclay, Inserm, Physiologie et Physiopathologie Endocriniennes, Le Kremlin-Bicêtre, France; 11Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre, Service d’Endocrinologie Pédiatrique, Centre de Référence des Maladies Rares du Métabolisme du Calcium et du Phosphate, filaire OSCAR, Le Kremlin-Bicêtre, France
Context: In patients with hypoparathyroidism refractory to conventional treatment, recombinant human (rh)PTH(1-84) or rhPTH(1-34) can be used as second-line therapy and effectively control hypocalcaemia. However, whether rhPTH replacement therapy is safe in the long term is unclear. Our objective was to assess bone effects of long-term therapy of chronic hypoparathyroidism with rhPTH(1-34).
Methods: We conducted a monocenter retrospective cross-sectional study at a tertiary university hospital in France. Eligible patients were adults with chronic hypoparathyroidism receiving rhPTH(1-34) therapy uninterruptedly for more than 24 months, who underwent a two-phase whole-body technetium-99m methyldiphosphonate scintigraphy. Clinical and biochemical data were collected retrospectively, covering the period of exposure to rhPTH(1-34) from its initiation until the date of the bone scintigraphy. Images were analyzed blindly by two experts using a visual grading to calculate a total composite score of the bone scan.
Results: 17 patients (13 women) were studied, with a median age of 42 [29;58] years. Median treatment duration was 55 [33;68] months and mean daily dose of rhPTH(1-34) was 37.5 [22.1;40] μg. Pathological bone uptake appearing like so-called “super bone scan” was detected in 10 (59%) patients, despite adequate calcemic control (median calcaemia over the study 2.10 [2.04;2.28] mmol/L). Patients with hypermetabolic bone scan received higher daily doses of rhPTH(1-34) compared with patients normal scan (21.0 vs 39.3 mg/day, P=0.0380). There was no difference in reported osteoarticular pain, in total and albumin-adjusted calcium concentration, in phosphate concentration, in calcium-phosphate product and in 24-hour urinary calcium excretion between the two groups. Patients with pathological bone scan compared with those with normal scan had higher osteocalcin (29.2 vs 232 ng/ml, P=0.0012), alkaline phosphatase (81 vs 112 UI/L, P=0.0094) and crosslaps (0.67 vs 3.83 ng/ml, P=0.0198). The total composite score correlated with osteocalcin (rs= 0.79, P=0.0002), alkaline phosphatase (rs= 0.83, P=0.0001), with crosslaps (rs= 0.51, P=0.045) and tended to correlate with mean daily rhPTH(1-34) dose (rs=0.44, P=0.0769). Osteocalcin concentration ≥ 87 ng/ml predicted a pathological bone uptake with 100% sensitivity and 85.7% specificity.
Discussion: Abnormally increased metabolic activity of the bone may occur under long-term PTH(1-34) therapy despite adequate calcaemic control, possibly due to the pharmacokinetics of this treatment. Bone scintigraphy can be useful in detecting iatrogenic hyperparathyroidism in patients receiving rhPTH(1–34) or rhPTH(1–84). Increased osteocalcin concentrations reliably predict bone cell overstimulation and should be used as biochemical marker for dose adjustment or treatment interruption.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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