{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:18:37Z","timestamp":1791296317932,"version":"4.1.0"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2024,5,27]],"date-time":"2024-05-27T00:00:00Z","timestamp":1716768000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,6,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Skeletal anomalies represent a characteristic feature of type 1 Gaucher disease (GD1). Here we evaluated the impact of an integrated therapy comprising enzyme-replacement therapy (ERT), cholecalciferol, and a normocalcemic-normocaloric-hyposodic diet (bone diet) on bone health in GD1 patients. We also performed a systematic review to compare our results with available data. From January 1, 2015 to February 28, 2019, all GD1 patients referred to Federico II University were enrolled and treated with the integrated therapy. Bone turnover markers and bone mineral density (BMD) were evaluated at baseline (T0) and after 24\u00a0months (T24). We enrolled 25 GD1 patients, all showing 25-hydroxy vitamin D (25OHD) levels &amp;lt; 50\u00a0nmol\/l (hypovitaminosis D) at T0. Response to cholecalciferol treatment was effective, showing a direct relationship between 25OHD levels before and after treatment. At T0, 2 GD1 patients showed fragility fractures, 5 the Erlenmeyer flask deformity, 3 osteonecrosis, and 7 a BMD Z-score\u2009\u2264\u2009\u20132. Overall, GD1 patients with bone anomalies showed higher C-terminal telopeptide levels compared with those without bone anomalies. No new bone anomalies occurred during 2 years of follow-up. At T24, BMD remained stable across the entire study cohort, including in patients with bone anomalies. The systematic review showed that our study is the first that evaluated all bone health parameters. Hypovitaminosis D is prevalent in GD1 patients. The response to cholecalciferol treatment was effective but different to healthy subjects and in patients with metabolic bone disorders. Integrated therapy including ERT, cholecalciferol, and bone diet guarantees bone health.<\/jats:p>","DOI":"10.1093\/jbmrpl\/ziae071","type":"journal-article","created":{"date-parts":[[2024,5,27]],"date-time":"2024-05-27T10:00:57Z","timestamp":1716804057000},"source":"Crossref","is-referenced-by-count":5,"title":["Imiglucerase, cholecalciferol, and bone-diet in skeletal health management of type I Gaucher disease patients: a pilot study and systematic review"],"prefix":"10.1093","volume":"8","author":[{"given":"Antonio","family":"Barbato","sequence":"first","affiliation":[{"name":"Federico II University of Naples Department of Clinical Medicine and Surgery, , 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"Vergatti","sequence":"additional","affiliation":[{"name":"Federico II University of Naples Department of Clinical Medicine and Surgery, , 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfonso","family":"Giaquinto","sequence":"additional","affiliation":[{"name":"Federico II University of Naples Department of Clinical Medicine and Surgery, , 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria Libera","family":"Pizzulo","sequence":"additional","affiliation":[{"name":"Federico II University of Naples Department of Clinical Medicine and Surgery, , 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludovica","family":"Perna","sequence":"additional","affiliation":[{"name":"Federico II University of Naples Department of Clinical Medicine and Surgery, , 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Perruolo","sequence":"additional","affiliation":[{"name":"Federico II University of Naples Department of Translational Medical Sciences, , 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Abate","sequence":"additional","affiliation":[{"name":"Federico II University of Naples Department of Clinical Medicine and Surgery, , 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelina","family":"Sibilio","sequence":"additional","affiliation":[{"name":"Santobono-Pausilipon Children's Hospital Metabolic Diseases Unit, , 80129 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ciro","family":"Mainolfi","sequence":"additional","affiliation":[{"name":"Federico II University of Naples Department of Advanced Biomedical Sciences, , 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernesto","family":"Soscia","sequence":"additional","affiliation":[{"name":"Institute of Biostructures and Bioimaging of the National Research Council \u2013 CNR , 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianpaolo","family":"De Filippo","sequence":"additional","affiliation":[{"name":"Assistance Publique-H\u00f4pitaux de Paris, H\u00f4pital Robert-Debr\u00e9, Service d\u2019Endocrinologie-Diab\u00e9tologie , 75019 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Formisano","sequence":"additional","affiliation":[{"name":"Federico II University of Naples Department of Translational Medical Sciences, , 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferruccio","family":"Galletti","sequence":"additional","affiliation":[{"name":"Federico II University of Naples Department of Clinical Medicine and Surgery, , 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pasquale","family":"Strazzullo","sequence":"additional","affiliation":[{"name":"Former Professor of Internal Medicine , Federico II University, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenico","family":"Rendina","sequence":"additional","affiliation":[{"name":"Federico II University of Naples Department of Clinical Medicine and Surgery, , 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,5,27]]},"reference":[{"key":"2024071308063307500_ref1","author":"Pastores","year":"1993\u20132023"},{"issue":"5","key":"2024071308063307500_ref2","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1002\/ajmg.a.63132","article-title":"Nosology of genetic skeletal disorders: 2023 revision","volume":"191","author":"Unger","year":"2023","journal-title":"Am J Med Genet A"},{"key":"2024071308063307500_ref3","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.ejim.2022.11.028","article-title":"Similarities and differences between Gaucher disease and acid sphingomyelinase deficiency: an algorithm to support the diagnosis","volume":"108","author":"Cappellini","year":"2023","journal-title":"Eur J Intern Med"},{"issue":"11","key":"2024071308063307500_ref4","doi-asserted-by":"crossref","first-page":"5538","DOI":"10.3390\/ijms22115538","article-title":"Accurate molecular diagnosis of Gaucher disease using clinical exome sequencing as a first-tier test","volume":"22","author":"Zampieri","year":"2021","journal-title":"Int J Mol Sci"},{"issue":"3","key":"2024071308063307500_ref5","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1177\/10600280221108443","article-title":"A systematic review and meta-analyses of longitudinal studies on drug treatments for Gaucher disease","volume":"57","author":"Leonart","year":"2023","journal-title":"Ann Pharmacother"},{"issue":"18","key":"2024071308063307500_ref6","doi-asserted-by":"crossref","first-page":"2835","DOI":"10.1001\/archinte.160.18.2835","article-title":"The Gaucher registry: demographics and disease characteristics of 1698 patients with Gaucher disease","volume":"160","author":"Charrow","year":"2000","journal-title":"Arch Intern Med"},{"issue":"6","key":"2024071308063307500_ref7","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1007\/s00223-014-9923-y","article-title":"Gaucher disease and bone manifestations","volume":"95","author":"Marcucci","year":"2014","journal-title":"Calcif Tissue Int"},{"issue":"12","key":"2024071308063307500_ref8","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1007\/s12325-014-0174-0","article-title":"Management of bone disease in Gaucher disease type 1: clinical practice","volume":"31","author":"Giuffrida","year":"2014","journal-title":"Adv Ther"},{"issue":"1","key":"2024071308063307500_ref9","doi-asserted-by":"crossref","first-page":"74","DOI":"10.3390\/nu14010074","article-title":"Nutrition, physical activity, and dietary supplementation to prevent bone mineral density loss: a food pyramid","volume":"14","author":"Rondanelli","year":"2021","journal-title":"Nutrients"},{"issue":"3","key":"2024071308063307500_ref10","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1056\/NEJMra070553","article-title":"Vitamin D deficiency","volume":"357","author":"Holick","year":"2007","journal-title":"N Engl J Med"},{"issue":"3","key":"2024071308063307500_ref11","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1093\/ndt\/gfn548","article-title":"Association between metabolic syndrome and nephrolithiasis in an inpatient population in southern Italy: role of gender, hypertension and abdominal obesity","volume":"24","author":"Rendina","year":"2009","journal-title":"Nephrol Dial Transplant"},{"issue":"1","key":"2024071308063307500_ref12","doi-asserted-by":"crossref","first-page":"17101","DOI":"10.1038\/nrdp.2017.101","article-title":"Rickets","volume":"3","author":"Carpenter TO","year":"2017","journal-title":"Nat Rev Dis Primers"},{"issue":"3","key":"2024071308063307500_ref13","doi-asserted-by":"crossref","first-page":"105","DOI":"10.4008\/jcrpe.v1i3.53","article-title":"Controversies in the definition and treatment of idiopathic short stature (ISS)","volume":"1","author":"Pedicelli","year":"2009","journal-title":"J Clin Res Pediatr Endocrinol"},{"issue":"4","key":"2024071308063307500_ref14","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1007\/s40292-023-00587-0","article-title":"Low potassium intake: a common risk factor for nephrolithiasis in patients with high blood pressure","volume":"30","author":"Abate","year":"2023","journal-title":"High Blood Press Cardiovasc Prev"},{"issue":"3","key":"2024071308063307500_ref15","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1210\/jc.2005-1606","article-title":"Fibroblast growth factor 23 is increased in calcium nephrolithiasis with hypophosphatemia and renal phosphate leak","volume":"91","author":"Rendina","year":"2006","journal-title":"J Clin Endocrinol Metab"},{"issue":"1","key":"2024071308063307500_ref16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4081\/reumatismo.2016.870","article-title":"Guidelines for the diagnosis, prevention and management of osteoporosis","volume":"68","author":"Rossini","year":"2016","journal-title":"Reumatismo"},{"issue":"19","key":"2024071308063307500_ref17","doi-asserted-by":"crossref","first-page":"4148","DOI":"10.3390\/nu14194148","article-title":"Definition, assessment, and management of vitamin D inadequacy: suggestions, recommendations, and warnings from the Italian Society for Osteoporosis, Mineral Metabolism and Bone Diseases (SIOMMMS)","volume":"14","author":"Bertoldo","year":"2022","journal-title":"Nutrients"},{"issue":"4","key":"2024071308063307500_ref18","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1007\/s00223-019-00578-1","article-title":"Vitamin D status in Paget disease of bone and efficacy-safety profile of cholecalciferol treatment in Pagetic patients with hypovitaminosis D","volume":"105","author":"Rendina","year":"2019","journal-title":"Calcif Tissue Int"},{"key":"2024071308063307500_ref19","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1053\/j.seminhematol.2004.07.009","article-title":"Therapeutic goals in the treatment of Gaucher disease","volume":"41","author":"Pastores","year":"2004","journal-title":"Semin Hematol"},{"issue":"7","key":"2024071308063307500_ref20","doi-asserted-by":"crossref","first-page":"2256","DOI":"10.1093\/ndt\/gfq664","article-title":"Characteristic clinical and biochemical profile of recurrent calcium-oxalate nephrolithiasis in patients with metabolic syndrome","volume":"26","author":"Rendina","year":"2011","journal-title":"Nephrol Dial Transplant"},{"issue":"15","key":"2024071308063307500_ref21","doi-asserted-by":"crossref","first-page":"3180","DOI":"10.3390\/nu14153180","article-title":"Evaluation of the nutritional status of Gaucher disease type I patients under enzyme replacement treatment","volume":"14","author":"Iaccarino Idelson","year":"2022","journal-title":"Nutrients"},{"issue":"11","key":"2024071308063307500_ref22","first-page":"838","article-title":"Bone crises in Gaucher disease","volume":"5","author":"Cohen","year":"2003","journal-title":"Isr Med Assoc J"},{"issue":"6","key":"2024071308063307500_ref23","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1002\/jbmr.3734","article-title":"Gaucher disease in bone: from pathophysiology to practice","volume":"34","author":"Hughes","year":"2019","journal-title":"J Bone Miner Res"},{"key":"2024071308063307500_ref24","doi-asserted-by":"crossref","first-page":"e1000100","DOI":"10.1371\/journal.pmed.1000100","article-title":"The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration","volume":"6","author":"Liberati","year":"2009","journal-title":"PLoS Med"},{"issue":"12","key":"2024071308063307500_ref25","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1016\/j.pmrj.2012.10.013","article-title":"Dealing with non-normal data","volume":"4","author":"Sainani","year":"2012","journal-title":"PM R"},{"key":"2024071308063307500_ref26","first-page":"27","article-title":"Prevalence of four lysosomal storage diseases in primary care in Italy","volume":"2","author":"Carubbi","year":"2019","journal-title":"Rivista SIMG"},{"issue":"2","key":"2024071308063307500_ref27","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1006\/bcmd.2002.0517","article-title":"Decreased bone density in splenectomized Gaucher patients receiving enzyme replacement therapy","volume":"28","author":"Schiffmann","year":"2002","journal-title":"Blood Cells Mol Dis"},{"issue":"5","key":"2024071308063307500_ref28","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1007\/s10545-005-0032-y","article-title":"Gaucher disease and bone: laboratory and skeletal mineral density variations during a long period of enzyme replacement therapy","volume":"28","author":"Ciana","year":"2005","journal-title":"J Inherit Metab Dis"},{"issue":"1","key":"2024071308063307500_ref29","first-page":"31","article-title":"Body composition and bone metabolism in young Gaucher disease type I patients treated with imiglucerase","volume":"13","author":"Parisi","year":"2008","journal-title":"Eur J Med Res"},{"key":"2024071308063307500_ref30","doi-asserted-by":"crossref","first-page":"2069","DOI":"10.2147\/TCRM.S177480","article-title":"Gene variants of osteoprotegerin, estrogen-, calcitonin- and vitamin D-receptor genes and serum markers of bone metabolism in patients with Gaucher disease type 1","volume":"14","author":"Zimmermann","year":"2018","journal-title":"Ther Clin Risk Manag"},{"issue":"3","key":"2024071308063307500_ref31","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.ymgme.2008.12.001","article-title":"Patients with Gaucher disease living in England show a high prevalence of vitamin D insufficiency with correlation to osteodensitometry","volume":"96","author":"Mikosch","year":"2009","journal-title":"Mol Genet Metab"},{"key":"2024071308063307500_ref32","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.bcmd.2016.10.008","article-title":"Management goals for type 1 Gaucher disease: an expert consensus document from the European working group on Gaucher disease","volume":"68","author":"Biegstraaten","year":"2018","journal-title":"Blood Cells Mol Dis"},{"issue":"3-5","key":"2024071308063307500_ref33","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.jsbmb.2011.05.003","article-title":"The ratio of serum 24,25-dihydroxyvitamin D(3) to 25-hydroxyvitamin D(3) is predictive of 25-hydroxyvitamin D(3) response to vitamin D(3) supplementation","volume":"126","author":"Wagner","year":"2011","journal-title":"J Steroid Biochem Mol Biol"},{"issue":"3","key":"2024071308063307500_ref34","doi-asserted-by":"crossref","first-page":"392","DOI":"10.3803\/EnM.2021.1349","article-title":"Interplay of vitamin D and CYP3A4 polymorphisms in endocrine disorders and cancer","volume":"37","author":"Kasarla","year":"2022","journal-title":"Endocrinol Metab (Seoul)"},{"issue":"1","key":"2024071308063307500_ref35","doi-asserted-by":"crossref","first-page":"6974","DOI":"10.1038\/s41598-019-43462-6","article-title":"The dynamic relationships between the active and catabolic vitamin D metabolites, their ratios, and associations with PTH","volume":"9","author":"Tang","year":"2019","journal-title":"Sci Rep"},{"issue":"8","key":"2024071308063307500_ref36","doi-asserted-by":"crossref","first-page":"1839","DOI":"10.1002\/jbmr.1680","article-title":"Risk factors for fractures and avascular osteonecrosis in type 1 Gaucher disease: a study from the international collaborative Gaucher group (ICGG) Gaucher registry","volume":"27","author":"Khan","year":"2012","journal-title":"J Bone Miner Res"},{"key":"2024071308063307500_ref37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.clinbiochem.2022.09.002","article-title":"Current use of bone turnover markers in the management of osteoporosis","volume":"109-110","author":"Brown","year":"2022","journal-title":"Clin Biochem"},{"issue":"1","key":"2024071308063307500_ref38","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.jocd.2019.03.004","article-title":"Consensus statement on the use of bone turnover markers for short-term monitoring of osteoporosis treatment in the Asia-Pacific region","volume":"24","author":"Wu","year":"2021","journal-title":"J Clin Densitom"},{"issue":"4","key":"2024071308063307500_ref39","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1210\/jc.2008-1832","article-title":"Relationships of serum 25-hydroxyvitamin D to bone mineral density and serum parathyroid hormone and markers of bone turnover in older persons","volume":"94","author":"Kuchuk","year":"2009","journal-title":"J Clin Endocrinol Metab"},{"issue":"4","key":"2024071308063307500_ref40","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/S2213-8587(13)70212-2","article-title":"The effect of vitamin D supplementation on skeletal, vascular, or cancer outcomes: a trial sequential meta-analysis [published correction appears in lancet diabetes Endocrinol]","volume":"2","author":"Bolland","year":"2014","journal-title":"Lancet Diabetes Endocrinol"},{"issue":"1","key":"2024071308063307500_ref41","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1007\/s00198-011-1752-5","article-title":"The effect of high-dose vitamin D on bone mineral density and bone turnover markers in postmenopausal women with low bone mass\u2014a randomized controlled 1-year trial","volume":"23","author":"Grimnes","year":"2012","journal-title":"Osteoporos Int"},{"key":"2024071308063307500_ref42","doi-asserted-by":"crossref","first-page":"1307896","DOI":"10.3389\/fnut.2023.1307896","article-title":"Vitamin D status and its associations with bone mineral density, bone turnover markers, and parathyroid hormone in Chinese postmenopausal women with osteopenia and osteoporosis","volume":"10","author":"Chen","year":"2024","journal-title":"Front Nutr"},{"issue":"23-24","key":"2024071308063307500_ref43","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1007\/s10354-010-0841-y","article-title":"An overview on bone manifestations in Gaucher disease","volume":"160","author":"Mikosch","year":"2010","journal-title":"Wien Med Wochenschr"},{"issue":"2","key":"2024071308063307500_ref44","doi-asserted-by":"crossref","DOI":"10.1016\/j.gim.2022.10.011","article-title":"Long-term effects of eliglustat on skeletal manifestations in clinical trials of patients with Gaucher disease type 1","volume":"25","author":"Cox","year":"2023","journal-title":"Genet Med"},{"issue":"11","key":"2024071308063307500_ref45","doi-asserted-by":"crossref","first-page":"1801","DOI":"10.1002\/jbmr.5650111125","article-title":"Bone density in type 1 Gaucher disease","volume":"11","author":"Pastores","year":"1996","journal-title":"J Bone Miner Res"},{"issue":"2","key":"2024071308063307500_ref46","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.ecl.2010.02.001","article-title":"Osteomalacia as a result of vitamin D deficiency","volume":"39","author":"Bhan","year":"2010","journal-title":"Endocrinol Metab Clin N Am"},{"issue":"13","key":"2024071308063307500_ref47","doi-asserted-by":"crossref","first-page":"1660","DOI":"10.1503\/cmaj.071416","article-title":"Change in bone mineral density as a function of age in women and men and association with the use of antiresorptive agents","volume":"178","author":"Berger","year":"2008","journal-title":"CMAJ"}],"container-title":["JBMR Plus"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jbmrplus\/advance-article-pdf\/doi\/10.1093\/jbmrpl\/ziae071\/57925310\/ziae071.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jbmrplus\/article-pdf\/8\/8\/ziae071\/58532383\/ziae071.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jbmrplus\/article-pdf\/8\/8\/ziae071\/58532383\/ziae071.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,13]],"date-time":"2024-07-13T08:07:07Z","timestamp":1720858027000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jbmrplus\/article\/doi\/10.1093\/jbmrpl\/ziae071\/7683017"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,27]]},"references-count":47,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2024,6,29]]}},"URL":"https:\/\/doi.org\/10.1093\/jbmrpl\/ziae071","relation":{},"ISSN":["2473-4039"],"issn-type":[{"value":"2473-4039","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,8]]},"published":{"date-parts":[[2024,5,27]]},"article-number":"ziae071"}}