Endocrine Abstracts (2014) 36 P18 | DOI: 10.1530/endoabs.36.P18

Suppression of bone turnover and its determinants in children receiving bisphosphonate therapy

Andreas Kyriakou1, Jane D McNeilly2, Martin McMillan1, M Guftar Shaikh1, Avril Mason1 & S Faisal Ahmed1

1Developmental Endocrinology Research Group, Royal Hospital for Sick Children, University of Glasgow, Glasgow, UK; 2Department of Biochemistry, Royal Hospital for Sick Children, Glasgow, UK.

Introduction: Bisphosphonate therapy (BPT) reduces osteoclast activity and may be associated with adynamic bone turnover. The extent of suppression of bone turnover and its determinants are unclear.

Methods: Markers of bone metabolism were evaluated in 15 children (9M/6F) receiving cyclical BPT intravenously for osteoporosis. The median age at first biochemical assessment was 10.8 years (0.16, 16.3). Serum type I collagen cross-linked C-telopeptide (CTX), alkaline phosphatase (ALP), calcium (CA), phosphate (P), parathyroid hormone (PTH) and 25 hydroxy vitamin D (VitD) were measured on day 1 of each BPT cycle. The CTX was expressed as a centile of the reference range in healthy children. The results are presented in Table 1.

Results: The median interval between the first BPT cycle and first biochemical assessment was 0.67 years (0.15, 8.12). The median duration of observation was 1.1 years (0.58, 3.3) and the median number of samples per patient was 5 (2, 8).

The median CTX centile was 2.4 (0.5, 7.1), thus below 10th centile, throughout the duration of observation (P<0.0001). ALP was negatively correlated with the duration of treatment (r−0.35, P<0.05) and positively correlated with CTX (r=0.72, P<0.0001). Median CTX in patients with (n, 4) and without (n, 11) consistently low VitD was 2.61 (1.3, 5.1) and 1.96 (0.34, 3.6) (P<0.05). Median ALP in the same two groups was 302 U/l (180, 455) and 141 U/l (36, 500) (P<0.0001). PTH was positively correlated with CTX (r=0.51, P<0.05).

Table 1
Time since start BPT (years)
Reference range0.511.523>3
CTX centile2.8 (0.7,4.1)2.8 (0.6,4.9)2.7 (0.5,3.8)2.8 (0.5,5.5)2.1 (1.4,7.1)2.1 (1.0,4.9)
ALP (U/l)60–424351 (62,500)261 (49,421)192 (36,455)141 (39,396)215 (136,346)145 (105,274)
PTH (pmol/l)1.6–7.52.9 (1.4,4.5)2.35 (1.0,6.9)3.35 (2.8,6.0)3.4 (2.1, 7.8)2.95 (2.5,5.1)4.3 (2.8,5.6)
VitD (nmol/l)>5047 (26,78)36 (19,108)15 (14,44)23 (14,36)31 (23,38)57 (34,98)
Values:median (range)

Conclusion: Bone resorption is markedly suppressed compared to bone formation. Vitamin D and PTH status influence the extent of suppression of bone turnover. An assessment of bone turnover markers may allow improved titration of BPT.

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