Bisphosphonate therapy for spinal osteoporosis in Hajdu-Cheney syndrome – new data and literature review
Abstract Background Hajdu-Cheney syndrome (HCS) (#OMIM 102500) is a rare, autosomal dominant condition that presents in early childhood. It is caused by mutations in the terminal exon of NOTCH2, which encodes the transmembrane NOTCH2 receptor. This pathway is involved in the coupled processes of bon...
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| Format: | Article |
| Language: | English |
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BMC
2018-04-01
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| Series: | Orphanet Journal of Rare Diseases |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13023-018-0795-5 |
| _version_ | 1819077015605608448 |
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| author | James F. H. Pittaway Christopher Harrison Yumie Rhee Muriel Holder-Espinasse Alan E. Fryer Tim Cundy William M. Drake Melita D. Irving |
| author_facet | James F. H. Pittaway Christopher Harrison Yumie Rhee Muriel Holder-Espinasse Alan E. Fryer Tim Cundy William M. Drake Melita D. Irving |
| author_sort | James F. H. Pittaway |
| collection | DOAJ |
| description | Abstract Background Hajdu-Cheney syndrome (HCS) (#OMIM 102500) is a rare, autosomal dominant condition that presents in early childhood. It is caused by mutations in the terminal exon of NOTCH2, which encodes the transmembrane NOTCH2 receptor. This pathway is involved in the coupled processes of bone formation and resorption. The skeletal features of HCS include acro-osteolysis of the digits and osteoporosis commonly affecting vertebrae and long bones. Fractures are a prominent feature and are associated with significant morbidity. There is no specific treatment, but with both acro-osteolysis and generalized osteoporosis, it is possible that anti-resorptive treatment might be of benefit. However, to date only a few case reports have evaluated the effectiveness of bisphosphonate treatment. Methods We describe the clinical features, treatment regimens and response to bisphosphonate treatment in 7 newly described patients aged 6–39 with HCS, and pooled the data with that from 8 previously published cases (a total of 17 courses of treatment in 15 individuals). Results The mean lumbar spine bone mineral density (BMD) z-score before treatment was − 2.9 (SD 1.2). In 14 courses of treatment (82%), there was an increase in BMD with bisphosphonate treatment, but the impact (in terms of change in spinal BMD z-score) appeared to be less with advancing age (p = 0.01). There was no evidence that acro-osteolysis was prevented. Conclusions Although individual response is variable and age-related, the data support a role for bisphosphonates in preventing or treating spinal osteoporosis in HCS, but bone loss from the lumbar spine may be rapid after cessation. |
| first_indexed | 2024-12-21T18:50:29Z |
| format | Article |
| id | doaj.art-7137234905074ce4b6caf9d31248decd |
| institution | Directory Open Access Journal |
| issn | 1750-1172 |
| language | English |
| last_indexed | 2024-12-21T18:50:29Z |
| publishDate | 2018-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj.art-7137234905074ce4b6caf9d31248decd2022-12-21T18:53:46ZengBMCOrphanet Journal of Rare Diseases1750-11722018-04-011311710.1186/s13023-018-0795-5Bisphosphonate therapy for spinal osteoporosis in Hajdu-Cheney syndrome – new data and literature reviewJames F. H. Pittaway0Christopher Harrison1Yumie Rhee2Muriel Holder-Espinasse3Alan E. Fryer4Tim Cundy5William M. Drake6Melita D. Irving7Department of Endocrinology, St Bartholomew’s HospitalDepartment of Clinical Genetics, Alder Hey Children’s NHS Foundation TrustDepartment of Internal Medicine, Severance Hospital, Endocrine Research Institute, Yonsei University College of MedicineDepartment of Clinical Genetics, Guy’s and St Thomas’ NHS Foundation TrustDepartment of Clinical Genetics, Liverpool Women’s NHS Foundation TrustDepartment of Medicine, University of AucklandDepartment of Endocrinology, St Bartholomew’s HospitalDepartment of Clinical Genetics, Guy’s and St Thomas’ NHS Foundation TrustAbstract Background Hajdu-Cheney syndrome (HCS) (#OMIM 102500) is a rare, autosomal dominant condition that presents in early childhood. It is caused by mutations in the terminal exon of NOTCH2, which encodes the transmembrane NOTCH2 receptor. This pathway is involved in the coupled processes of bone formation and resorption. The skeletal features of HCS include acro-osteolysis of the digits and osteoporosis commonly affecting vertebrae and long bones. Fractures are a prominent feature and are associated with significant morbidity. There is no specific treatment, but with both acro-osteolysis and generalized osteoporosis, it is possible that anti-resorptive treatment might be of benefit. However, to date only a few case reports have evaluated the effectiveness of bisphosphonate treatment. Methods We describe the clinical features, treatment regimens and response to bisphosphonate treatment in 7 newly described patients aged 6–39 with HCS, and pooled the data with that from 8 previously published cases (a total of 17 courses of treatment in 15 individuals). Results The mean lumbar spine bone mineral density (BMD) z-score before treatment was − 2.9 (SD 1.2). In 14 courses of treatment (82%), there was an increase in BMD with bisphosphonate treatment, but the impact (in terms of change in spinal BMD z-score) appeared to be less with advancing age (p = 0.01). There was no evidence that acro-osteolysis was prevented. Conclusions Although individual response is variable and age-related, the data support a role for bisphosphonates in preventing or treating spinal osteoporosis in HCS, but bone loss from the lumbar spine may be rapid after cessation.http://link.springer.com/article/10.1186/s13023-018-0795-5BisphosphonatesDiseasesGenetic disordersHuman studiesDual energy x-ray absorptiometry (DEXA) |
| spellingShingle | James F. H. Pittaway Christopher Harrison Yumie Rhee Muriel Holder-Espinasse Alan E. Fryer Tim Cundy William M. Drake Melita D. Irving Bisphosphonate therapy for spinal osteoporosis in Hajdu-Cheney syndrome – new data and literature review Orphanet Journal of Rare Diseases Bisphosphonates Diseases Genetic disorders Human studies Dual energy x-ray absorptiometry (DEXA) |
| title | Bisphosphonate therapy for spinal osteoporosis in Hajdu-Cheney syndrome – new data and literature review |
| title_full | Bisphosphonate therapy for spinal osteoporosis in Hajdu-Cheney syndrome – new data and literature review |
| title_fullStr | Bisphosphonate therapy for spinal osteoporosis in Hajdu-Cheney syndrome – new data and literature review |
| title_full_unstemmed | Bisphosphonate therapy for spinal osteoporosis in Hajdu-Cheney syndrome – new data and literature review |
| title_short | Bisphosphonate therapy for spinal osteoporosis in Hajdu-Cheney syndrome – new data and literature review |
| title_sort | bisphosphonate therapy for spinal osteoporosis in hajdu cheney syndrome new data and literature review |
| topic | Bisphosphonates Diseases Genetic disorders Human studies Dual energy x-ray absorptiometry (DEXA) |
| url | http://link.springer.com/article/10.1186/s13023-018-0795-5 |
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