Calcium-PTH-vitamin D axis in older patients with hip fracture

Abstract

We read with interest the article by Sakuma and colleagues [1] dealing with the controversial issue of vitamin D-PTH status in hip fracture (HF) patients. With an ageing population and exponentially increasing numbers of HFs worldwide, it is important to clarify the contribution of abnormalities in calcium-PTH-vitamin D relationships to HFs. Adequate vitamin D-PTH status is paramount in calcium homeostasis and for bone health. However, recent large randomised controlled trials [2–4] as well as systemic reviews [5–7] contrary to a previous meta-analysis [8] did not find that supplementation with vitamin D and calcium reduces HFs, except in frail people confined to institutions [7]. Sakuma et al. [1] demonstrated that 62% of 50 HF patients had vitamin D insufficiency, defined as serum 25hydroxyvitamin D (25(OH)D) concentration less than 50 nmol/l, and this was associated with elevated PTH (>65 pg/ml) levels in 19.4%. We would like to add further evidence to support the harmful effects of abnormal CaPTH-vitamin D status in this population and emphasise some new dimensions to this topic. In 501 consecutive patients aged 60 years and older (mean 81.9±8.1 (SD) years, 73% females) admitted to our hospital with non-pathological minimal trauma HF we measured serum 25(OH)D, intact PTH, calcium, phosphate, magnesium, albumin, haemoglobin and creatinine; in 230 patients we also evaluated the bone turnover markers: serum osteocalcin (OC) and bone specific alkaline phosphatase (BAP) and urine deoxypyridinoline (DPD) and N-terminal cross-linking telopeptide of type I collagen (NTx). Demographic and clinical characteristics were prospectively recorded in all patients. Mean serum 25(OH)D concentration was 36.3±17.1 (SD) nmol/l. The prevalence of 25(OH)D insufficiency ( 6.5 pmol/l) indicating secondary hyperparathyroidism (SHPT), presented only in 45.7% of patients with 25(OH)D insufficiency, while in the other half of these patients the PTH level was in the normal range. A similar observation has been reported by Sahota et al. [12]. In Sakuma’s series, in about 80% of HF patients with 25(OH)D insufficiency the serum PTH level was not elevated. There was no correlation between PTH and 25 (OH)D levels in HF patients in both Sakuma’s (r=−0.17; p>0.05) and our study (r=−0.10; p=0.114) These findings demonstrate that in older HF patients, as well as in general in patients with osteoporosis [13–15], SHPT is not a universal response to hypovitaminosis D. In other words, contrary to the hypothesis that predicts increase in PTH secretion following decrease in serum 25(OH)D concentrations, the PTH level in 50% (whites) to 80% (Asians) of HF patients with vitamin D insufficiency remained in the normal range. This has been defined as “functional hypoparathyroidism” [12, 13]. These data show heterogeneity in the HF population in regard to the complex and still poorly understood vitamin D-PTH relationship. The mechanism underlying the defect in PTH response to vitamin D deficiency is unclear and may be related to an abnormality in the calcium-sensing receptor, which plays a central role in regulating PTH gene expression, PTH synthesis and secretion, and/or dysregulation in PTH gene transcription or Osteoporos Int (2007) 18:693–695 DOI 10.1007/s00198-006-0284-x