{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T01:07:05Z","timestamp":1780621625343,"version":"3.54.1"},"reference-count":21,"publisher":"Walter de Gruyter GmbH","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec id=\"j_jpem-2025-0652_abs_001\">\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>\n                      Lipoprotein receptor\u2013related protein-5 (\n                      <jats:italic>LRP5<\/jats:italic>\n                      )-related disorders are characterized by variably reduced vision and juvenile osteoporosis due to loss-of-function mutations in the low-density\n                      <jats:italic>LRP5<\/jats:italic>\n                      gene. Compelling evidence on effectiveness of bisphosphonate treatment in these disorders remains limited. We aimed to describe the phenotypic spectrum and clinical, densitometric, and fracture outcomes following zoledronate therapy in children with\n                      <jats:italic>LRP<\/jats:italic>\n                      5-related disorders.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_jpem-2025-0652_abs_002\">\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>\n                      Five patients (P1\u2013P5), referred at a median age of 9\u00a0years for recurrent low-impact fractures with confirmed\n                      <jats:italic>LRP5<\/jats:italic>\n                      mutations, were included. P1\u2013P3 were siblings with a homozygous c.1259\u202fG&gt;Cp.(Gly420Ala), variant of likely pathogenic. P4 carried compound heterozygous mutations for three sequence variants, including novel pathogenic variants c.2449\u202fC&gt;T p.(Arg817Cys), and c.362A&gt;Gp.(Lys121Arg), and P5 had a heterozygous c.4502C&gt;Tp.(Pro1501Leu) variant, also identified in the mother, a variant of uncertain significance (VUS). Four patients (P2\u2013P5) received zoledronate for a median duration of 2\u00a0years (range 1.5\u201311 years). Post-treatment, P2, P3, and P5 showed improvements in lumbar spine (LS) Bone Mineral Apparent Density (BMAD) Z-scores (+1.0, +0.7, and +2.7 respectively), remaining fracture-free. P4 exhibited an increase in LS BMAD (+0.3) and vertebral remodeling.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_jpem-2025-0652_abs_003\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      <jats:italic>LRP<\/jats:italic>\n                      5-related disorders should be considered in patients with recurrent fractures and visual involvement. Zoledronate appears effective in improving bone density, reducing fracture frequency, and promoting vertebral remodeling, although further studies are required to determine optimal treatment duration.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1515\/jpem-2025-0652","type":"journal-article","created":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T22:28:43Z","timestamp":1773786523000},"page":"499-507","source":"Crossref","is-referenced-by-count":0,"title":["<i>LRP5<\/i>\n                    -related primary osteoporosis: phenotypic spectrum and treatment response to zoledronic acid"],"prefix":"10.1515","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3015-4161","authenticated-orcid":false,"given":"Chamila","family":"Balagamage","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Diabetes , 1729 Birmingham Women\u2019s and Children\u2019s NHS Foundation Trust , Birmingham , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Proteek","family":"Sen","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Diabetes , 1729 Birmingham Women\u2019s and Children\u2019s NHS Foundation Trust , Birmingham , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Crabtree","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Diabetes , 1729 Birmingham Women\u2019s and Children\u2019s NHS Foundation Trust , Birmingham , UK"},{"name":"Department of Metabolism and Systems Science, College of Medical and Dental Sciences , University of Birmingham , Birmingham , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics , Birmingham Women\u2019s and Children\u2019s NHS Foundation Trust , Birmingham , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suma","family":"Uday","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Diabetes , 1729 Birmingham Women\u2019s and Children\u2019s NHS Foundation Trust , Birmingham , UK"},{"name":"Department of Metabolism and Systems Science, College of Medical and Dental Sciences , University of Birmingham , Birmingham , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2026,3,16]]},"reference":[{"key":"2026060500564535447_j_jpem-2025-0652_ref_001","doi-asserted-by":"crossref","unstructured":"Westendorf, JJ, Kahler, RA, Schroeder, TM. 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