Clin Rheumatol (2014) 33:733–735 DOI 10.1007/s10067-014-2577-3

LETTER TO THE EDITOR

Low bone density in achondroplasia Özlem Taşoğlu & Şule Şahin Onat & Didem Yenigün & Meryem Doğan Aslan & Güldal Funda Nakipoğlu & Neşe Özgirgin

Received: 25 February 2014 / Revised: 3 March 2014 / Accepted: 9 March 2014 / Published online: 25 March 2014 # Clinical Rheumatology 2014

To the editor, A 39-year-old female achondroplastic patient was admitted to our outpatient clinic for her back and lower extremity pain. Her height and weight were 125 cm and 38 kg, respectively (Fig. 1). She had a body mass index of 24.3 kg/m2. She had undergone leg lengthening on bilateral tibias when she was 12. On physical examination, she had bilateral paravertebral muscle spasm at her back. She also had painful hip internal rotation and knee flexion on both sides with bilateral positive Clarke’s sign. Her physical examination was otherwise noncontributory. X-ray examination revealed early degenerative changes, especially at the hip joints and strikingly osteopenia. On detailed questioning, it was understood that she had been advised to receive 300,000 IU vitamin D3 (the form of vitamin D available in our country) once a year and to exercise regularly for low bone density 2 years ago. The past two bone mineral density (BMD) measurements, performed by a single technician using dual-energy X-ray absorptiometry (DEXA) on a Lunar DPX-IQ scanner in our center, were analyzed, and a new BMD measurement was performed under similar conditions with the ones referred above (Table 1, Fig. 2). The laboratory tests was as follows: serum total calcium, 9.3 mg/dl (8.2–10.6); inorganic phosphate, 3.2 mg/dl (2.5–4.5); alkaline phosphatase (ALP), 47 U/l (30–126); type 1 collagen C terminal telopeptide (CTX), 0.253 (25–573); osteocalcin, 3.46 ng/ml (3.1–13.7); parathormone, 34.23 pg/ml (15–65), and vitamin D3, 20.1 ng/ml (>30). Risk factor examination for low bone density yielded no results. Low bone density was considered as a consequence of altered bone metabolism due to achondroplasia. She was prescribed 300,000 IU oral Ö. Taşoğlu (*) : Ş. Şahin Onat : D. Yenigün : M. Doğan Aslan : G. F. Nakipoğlu : N. Özgirgin Ankara Physical Medicine and Rehabilitation Training and Research Hospital, Ankara, Turkey e-mail: [email protected]

vitamin D3 and recommended to continue on her exercises. She was also included in a physical therapy program for her symptoms due to degenerative changes. Achondroplasia is the most common form of skeletal dysplasias. A spontan or inherited mutation in the fibroblast growth factor receptor 3 (FGFR3) gene on the fourth chromosome brings out the disease [1]. The primary defect is abnormal endochondral ossification [2]. It has a number of wellknown neuromusculoskeletal manifestations [3]. Recently, Arita et al. reported low bone density, diagnosed with spinal BMD analysis and panoramic radiographic measurements, in 5 of 11 achondroplastic patients for the first time in the literature [4]. To the best of our knowledge, our report is the second one referring the relationship between

Fig. 1 Our patient

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Table 1 BMD results of the patient for the last 3 years Year

Area

BMD (g/cm )

T score

Z score

2011

L1–L4 Femur neck L1–L4 Femur neck L1–L4 Femur neck

0.868 0.887 0.865 0.817 0.876 0.872

−2.6 −1.1 −2.7 −1.6 −2.6 −1.2

−1.6 −0.1 −1.7 −0.6 −1.7 −0.2

2012 2013

2

achondroplasia and low bone density. It is known that in achondroplasia, there are alterations in the length, structure, and diameter of the collagen fibers found in the cartilage and bone. Moreover, achondroplastics are known to have a decreased ALP level, which is a by-product of osteoblast activity

Fig. 2 The last BMD results of the patient

showing active bone formation [5, 6]. While the ALP level of our patient was normal, the CTX level was extremely low, and osteocalcin level was on the lower border of the reference values. Since CTX and osteocalcin are markers of bone turnover, the results of our patient are consistent with suppression of remodelling. Our case, for the first time in the literature, offers an insight into the mechanism of low bone density in achondroplastics. On the other hand, not only the possible defect in bone remodelling but probably also the limited participation to recreational activities because of the emotional and physical difficulties give way to low bone density in achondroplastic patients too. In conclusion, awareness, early diagnosis, and proper management of low bone density in this group of patients before osteoporosis development are important. Certainly, further large-scale studies should be performed to investigate the

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prevalence and molecular aspects of osteoporosis in achondroplastic patients. Disclosures None.

References 1. Rousseau F, Bonaventure J, Legeai-Mallet L, Pelet A, Rozet JM, Maroteaux P et al (1994) Mutations in the gene encoding fibroblast growth factor receptor-3 in achondroplasia. Nature 371(6494):252– 254

735 2. Laederich MB, Horton WA (2010) Achondroplasia: pathogenesis and implications for future treatment. Curr Opin Pediatr 22(4):516–523 3. Thompson NM, Hecht JT, Bohan TP, Kramer LA, Davidson K, Brandt ME et al (1999) Neuroanatomic and neuropsychological outcome in school-age children with achondroplasia. Am J Med Gen (Neuropsychiatr Genet) 88:145–153 4. Arita ES, Pippa MG, Marcucci M, Cardoso R, Cortes AR, Watanabe PC et al (2013) Assessment of osteoporotic alterations in achondroplastic patients: a case series. Clin Rheumatol 32(3):399–402 5. Stöss H, Pesch HJ (1985) Structural changes of collagen fibrils in skeletal dysplasias. Ultrastructural findings in the iliac crest. Virchows Arch A Pathol Anat Histopathol 405:341–364 6. Gutman AB (1959) Serum alkaline phosphatase activity in diseases of skeletal and hepatobiliary systems: consideration of current status. Am J Med 27:875–901