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      Alendronate treatment in cats with persistent ionized hypercalcemia: A retrospective cohort study of 20 cases

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          Abstract

          Background

          Limited information is available concerning treatment of ionized hypercalcemia in cats.

          Hypothesis/Objectives

          Describe clinical findings in a cohort of cats with persistent ionized hypercalcemia and evaluate long‐term tolerance and efficacy of alendronate in these patients.

          Animals

          Twenty cats with persistent ionized hypercalcemia of undetermined origin, presented for routine or referral consultation at the teaching hospital of Maisons‐Alfort (France).

          Methods

          Medical records were retrospectively reviewed. Cats were divided into Group 1 (cats that received alendronate as well as other treatments, n = 11) and Group 2 (cats that did not receive alendronate, n = 9). Survival analysis (Kaplan‐Meier method, log‐rank test, and Cox proportional hazard models) was conducted to compare time to selected outcomes.

          Results

          Azotemia was present in 15 cats (75%). Alendronate treatment was administered and well tolerated during the entire follow‐up period (median, 9.5 months; interquartile range [IQR], 6.3; 27) in all cats from Group 1, except in 1 cat that developed severe hypophosphatemia, prompting treatment discontinuation. Univariate analysis determined that alendronate treatment was significantly associated with shorter time to reach a 15% decrease in ionized calcium concentration (iCa) from baseline during follow‐up (119 days vs median not reached, P = .02). This association was no longer significant after adjustment for age and initial iCa.

          Conclusions and Clinical Importance

          Alendronate overall was well tolerated with chronic use in this cohort, and can be considered a treatment option for persistent ionized hypercalcemia in cats.

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          Most cited references44

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          Clinician’s Guide to Prevention and Treatment of Osteoporosis

          F Cosman, S. de Beur, M. S. LeBoff … (2014)
          The Clinician’s Guide to Prevention and Treatment of Osteoporosis was developed by an expert committee of the National Osteoporosis Foundation (NOF) in collaboration with a multispecialty council of medical experts in the field of bone health convened by NOF. Readers are urged to consult current prescribing information on any drug, device, or procedure discussed in this publication.
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            Esophagitis associated with the use of alendronate.

            Larry Stephenson, H Pinkas, G Tillotson … (1996)
            Alendronate, an aminobisphosphonate and a selective inhibitor of osteoclast-mediated bone resorption, is used to treat osteoporosis in postmenopausal women and Paget's disease of bone. Aminobiphosphonates can irritate the upper gastrointestinal mucosa. We describe three patients who had severe esophagitis shortly after starting to take alendronate and also analyze adverse esophageal effects reported to Merck, the manufacturer, through postmarketing surveillance. As of March 5, 1996, alendronate had been prescribed for an estimated 475,000 patients worldwide, and 1213 reports of adverse effects had been received. A total of 199 patients had adverse effects related to the esophagus; in 51 of these patients (26 percent), including the 3 we describe in case reports, adverse effects were categorized as serious or severe. Thirty-two patients (16 percent) were hospitalized, and two were temporarily disabled. Endoscopic findings generally indicated chemical esophagitis, with erosions or ulcerations and exudative inflammation accompanied by thickening of the esophageal wall. Bleeding was rare, and stomach or duodenal involvement unusual. In patients for whom adequate information was available, esophagitis seemed to be associated with swallowing alendronate with little or no water, lying down during or after ingestion of the tablet, lying down during or after ingestion of the tablet, continuing to take alendronate after the onset of symptoms, and having preexisting esophageal disorders. Alendronate can cause chemical esophagitis, including severe ulcerations, in some patients. Recommendations to reduce the risk of esophagitis include swallowing alendronate with 180 to 240 ml (6 to 8 oz) of water on arising in the morning, remaining upright for at least 30 minutes after swallowing the tablet and until the first food of the day has been ingested, and discontinuing the drug promptly if esophageal symptoms develop.
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              Bisphosphonates: a review of their pharmacokinetic properties.

              J.H. Lin (1996)
              Bisphosphonates are a unique class of drugs. As a family, they are characterized pharmacologically by their ability to inhibit bone resorption, whereas, pharmacokinetically, they are classified by their similarity in absorption, distribution, and elimination. Although all bisphosphonates have similar physicochemical properties, their antiresorbing activities differ substantially. Activity is dramatically increased when the amino group is contained in the aliphatic carbon chain. For example, alendronate, an aminobisphosphonate, is approximately 700-fold more potent than etidronate, both in vitro and in vivo. In general, bisphosphonates are poorly absorbed from the gastrointestinal tract as a result of their poor lipophilicity. In vitro and in vivo studies have shown that bisphosphonates are absorbed from the gastrointestinal tract via paracellular transport. Systemically available bisphosphonates disappear very rapidly from plasma, and are partly taken up by the bone and partly excreted by the kidney. The relative contribution of these two processes to overall plasma elimination differs significantly among bisphosphonates. To date, all bisphosphonates studied show no evidence of metabolism. Renal excretion is the only route of elimination. Studies with alendronate in rats indicate that the drug is actively secreted by an uncharacterized renal transport system, and not by the anionic or cationic renal transport systems. Bisphosphonates bind preferentially to bones which have high turnover rates, and their distribution in bone is not homogeneous. After bone uptake, the bisphosphonates are liberated again only when the bone in which they are deposited is resorbed. Thus, the half-life of bisphosphonates in bone is very long, ranging among different species from 1 to 10 years, depending largely on the rate of bone turnover.
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                Author and article information

                Contributors
                Maxime Kurtz:
                ORCID: https://orcid.org/0000-0003-4494-2975
                maxime.kurtz@vet-alfort.fr
                Journal
                Journal ID (nlm-ta): J Vet Intern Med
                Journal ID (iso-abbrev): J Vet Intern Med
                Journal ID (doi): 10.1111/(ISSN)1939-1676
                Journal ID (publisher-id): JVIM
                Title: Journal of Veterinary Internal Medicine
                Publisher: John Wiley & Sons, Inc. (Hoboken, USA )
                ISSN (Print): 0891-6640
                ISSN (Electronic): 1939-1676
                Publication date (Electronic): 01 October 2022
                Publication date (Print): Nov-Dec 2022
                Volume: 36
                Issue: 6 ( doiID: 10.1111/jvim.v36.6 )
                Pages: 1921-1930
                Affiliations
                [ 1 ] Department of Internal Medicine Ecole Nationale Vétérinaire d'Alfort Maisons‐Alfort France
                [ 2 ] Department of Clinical Epidemiology and Biostatistics Ecole Nationale Vétérinaire d'Alfort Maisons‐Alfort France
                [ 3 ] Ecole Nationale Vétérinaire d'Alfort Université Paris Est Créteil, INSERM, IMRB Maisons‐Alfort France
                Author notes
                [*] [* ] Correspondence

                Maxime Kurtz, Department of Internal Medicine, École Nationale Vétérinaire d'Alfort, 7, av. du Général de Gaulle, 94700 Maisons Alfort, France.

                Email: maxime.kurtz@ 123456vet-alfort.fr

                Author information
                https://orcid.org/0000-0003-4494-2975
                https://orcid.org/0000-0002-9263-1744
                https://orcid.org/0000-0003-3947-5655
                Article
                Publisher ID: JVIM16508
                DOI: 10.1111/jvim.16508
                PMC ID: 9708413
                PubMed ID: 36181368
                SO-VID: 8e000b40-ad8a-4c28-bcbe-0be192c32524
                Copyright © © 2022 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.
                License:

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 04 February 2022
                Date accepted : 19 July 2022
                Page count
                Figures: 3, Tables: 5, Pages: 10, Words: 7538
                Categories
                Subject: Standard Article
                Subject: SMALL ANIMAL
                Subject: Standard Articles
                Subject: Endocrinology
                Custom metadata
                source-schema-version-number 2.0
                cover-date November/December 2022
                details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_JATSPMC version:6.2.1 mode:remove_FC converted:29.11.2022

                ScienceOpen disciplines: Veterinary medicine
                Keywords: bisphosphonates,calcium,chronic kidney disease,urolithiasis
                Data availability:
                ScienceOpen disciplines: Veterinary medicine
                Keywords: bisphosphonates, calcium, chronic kidney disease, urolithiasis

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