Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2018 Apr 4;13(1):47.
doi: 10.1186/s13023-018-0795-5.

Bisphosphonate therapy for spinal osteoporosis in Hajdu-Cheney syndrome - new data and literature review

James F H Pittaway  1 , Christopher Harrison  2 , Yumie Rhee  3 , Muriel Holder-Espinasse  4 , Alan E Fryer  5 , Tim Cundy  6 , William M Drake  7 , Melita D Irving  4
Affiliations
Review

Bisphosphonate therapy for spinal osteoporosis in Hajdu-Cheney syndrome - new data and literature review

James F H Pittaway et al. Orphanet J Rare Dis. .

Erratum in

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.

Keywords: Bisphosphonates; Diseases; Dual energy x-ray absorptiometry (DEXA); Genetic disorders; Human studies.

PubMed Disclaimer

Conflict of interest statement

Ethics approval and consent to participate

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study formal consent is not required.

Consent for publication

Not applicable

Competing interests

Dr. Rhee reports personal fees from Amgen, personal fees from Eli Lilly, outside the submitted work. All other authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Sequential changes in lumbar spine z-score in one subject (case 2), treated with pamidronate from 8 to 10 years of age, and zoledronate at age 24. The increment in z-score was lower when she was treated as an adult. Between these two treatment periods her BMD z-score fell by 2.6 SD over 14 years
Fig. 2
Fig. 2
Scatterplot showing the negative correlation between change (Δ) in lumbar spine BMD z-score with bisphosphonate treatment in relation to the age at which treatment was started (17 courses of treatment in 15 individuals). Pearson correlation coefficient − 0.624 (p = 0.01). The new cases (from Table 1) are shown by green circles and the cases previously described in the literature (Table 2) are shown by red squares. The light blue triangle indicates the response in the patient described by Adami et al. [17] who was treated with denosumab for 2 years; the dark blue triangle the patient described by McKiernan [18] who was treated with both pamidronate and teriparatide for two years
Fig. 3
Fig. 3
Progression of acro-osteolysis despite treatment with bisphosphonates. Radiographs of the right index finger of subject 7, taken over 12 years. The timing of bisphosphonate treatment is indicated
See this image and copyright information in PMC

References

    1. Hajdu N, Kauntze R. Cranio-skeletal dysplasia. Br J Radiol. 1948;21(241):42–48. doi: 10.1259/0007-1285-21-241-42. - DOI - PubMed
    1. Cheney WD. Acro-Osteolysis. Am J Roentgenol Radium Therapy Nucl Med. 1965;94:595–607. - PubMed
    1. Albano LM, Bertola DR, Barba MF, Valente M, Robertson SP, Kim CA. Phenotypic overlap in Melnick-needles, serpentine fibula-polycystic kidney and Hajdu-Cheney syndromes: a clinical and molecular study in three patients. Clin Dysmorphol. 2007;16(1):27–33. doi: 10.1097/01.mcd.0000228418.74413.52. - DOI - PubMed
    1. Brennan AM, Pauli RM. Hajdu--Cheney syndrome: evolution of phenotype and clinical problems. Am J Med Genet. 2001;100(4):292–310. doi: 10.1002/1096-8628(20010515)100:4<292::AID-AJMG1308>3.0.CO;2-4. - DOI - PubMed
    1. Battelino N, Writzl K, Bratanic N, Irving MD, Novljan G. End-stage renal disease in an infant with Hajdu-Cheney syndrome. Ther Apher Dial. 2016;20(3):318–321. doi: 10.1111/1744-9987.12444. - DOI - PubMed