A variation in Bone Alkaline Phosphatase levels that correlates positively with bone loss and normal levels of aminoterminal propeptide of collagen I in girls with anorexia nervosa

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Abstract

Anorexia nervosa (AN) is a very extended pathology among adolescent girls nowadays. These patients show a high degree of osteopenia; hence, study of their bone remodelling is of great interest. Serum bone alkaline phosphatase (bAP) and aminoterminal propeptide of procollagen I (PINP) provide good sensitivity in the analysis of bone alterations in postmenopausal osteoporosis. The aim of this study was to compare the usefulness of bAP and PINP in the study of bone remodelling in AN, and their possible correlation with the degree of osteopenia in this pathology. In order to help in the interpretation of the results, levels of the β-isomer of urinary carboxyterminal propeptide of collagen I (β-CTX) have also been included. Serum bAP (IRMA) Tandem R-Ostase, Hybritech), PINP (RIA, Orion Diagnostica) and CTX (CrossLaps ELISA, Osteometer) were determined in 41 girls with AN, aged 18.5±2.2 years (mean±SD) and in 31 healthy control women, aged 19±2.3 years. Bone mineral density (BMD) in lumbar spine was measured by DEXA in the AN group. We found that 41 of the 43 patients had BMD z-scores under −2. No significant differences were found in the levels of serum bAP nor in PINP and β-CTX levels between controls and patients, although values in the AN group were highly variable. All the BMD z-score values were negative, and their absolute value correlates positively with bAP (P=0.0279) and almost with β-CTX (P=0.0921) but not with PINP (P=0.4627). Bone AP correlates with PINP in control girls (P=0.017), but not in the AN group (P=0.3573). Patients with AN were divided into three groups according to their levels of bAP: low (I), normal (II) or high (III). Patients with the highest bAP levels also presented the highest increase in bone resorption, according to their β-CTX levels, and the highest degree of osteopenia. However, values of PINP were similar in the three groups of patients. The bAP/β-CTX ratios in subgroups I, II and III of AN patients were 0.035, 0.065 and 0.073, a finding that suggests that bAP is not indicating the real degree of bone mineralization in these patients, because it is a contradiction that the formation/resorption ratio should be higher in the patients who have the highest bone loss. These results could suggest that bone loss in AN is produced by an increase in bone resorption (β-CTX), without variations in bone matrix formation (PINP); bAP levels are a good marker in the follow-up of osteopenia degree, but not a real indicator of bone mineralization, a similar situation to that of osteomalacia.

Introduction

The new assays for parameters of bone and collagen metabolism have generated much interest among researchers in the field of adult metabolic bone disease [1] and now are increasingly used by paediatricians. However, bone metabolism differs considerably between children and adults. Thus there is a specific paediatric perspective of bone metabolism and of the biochemical parameters used in its evaluation that must be taken into account together with the type of pathology under study [2].

With respect to biochemical markers of bone formation, in a recent report by our group [3] we found that among the available biochemical markers of osteoblast activity – total and bone alkaline phospatase (TAP and bAP, respectively), osteocalcin (BGP), procollagen I aminoterminal propeptide (PINP) and procollagen I carboxyterminal propeptide (PICP) – serum bAP and PINP showed the highest diagnostic accuracy for detecting the alterations in bone remodelling that take place in postmenopausal osteoporosis. In the field of biochemical markers of bone resorption, the new marker C-telopeptide of type I Collagen (CTX) has also demonstrated a high specificity and sensitivity in the study of bone turnover in this pathology [4]. In a recent work [5] we found that the urinary β-isomerized form of CTX is an adequate parameter to study bone resorption in anorexic adolescents.

Anorexia nervosa (AN) is a chronic eating disorder, characterised by self-imposed semistarvation, that affects 1% of adolescent females. Osteoporosis is one of the important medical complications associated with AN [6]. In spite of this fact, there are few and contradictory data available concerning bone turnover in this population [7]. The aim of this study was to compare the usefulness of bAP and PINP in the study of bone remodelling in AN and their possible correlation with the degree of osteopenia in this pathology. In order to help in the interpretation of the results, levels of urinary CTX of these patients have also been included.

Section snippets

Materials and methods

We studied 41 women with established AN, as defined by criteria of the American Psychiatric Association [8], with a mean age±standard deviation of 18.5±2.2 years (range 16–24 years) and 31 healthy control women, aged 19±2.3 years (range 16–24 years). The study was approved by the ethics committee of our hospital.

The AN group included women with amenorrhea (n=25), as well as those without amenorrhea who were on oral contraceptive treatment (n=16). The evolution time of AN was 3.9±1.8 years. Ten

Results

Table 1 shows the levels of serum bAP, PINP and urinary β-CTX in control girls and patients with AN. The degree of osteopenia expressed as the z-score of BMD in the anorexic group is also shown. All the patients showed BMD values under the mean value corresponding to their age (negative z-score). A high degree of osteopenia (mean value of z-score=−3.2) was observed in the anorexic group. With the exception of two patients whose values of z-score were −0.9 and −1.4, all the anorexic girls

Discussion

As can be expected, girls with AN presented a high degree of osteopenia compared with age-matched healthy girls. When we analysed the possible correlation between this observed osteopenia and the biochemical markers of bone formation bAP and PINP, we found a significant correlation with bAP, i.e. a greater bone loss corresponds to higher levels of bAP. However, there is no correlation between osteopenia and PINP levels. This correlation between bAP and BMD z-score could seem to be in

Acknowledgements

We wish to thank Dr. G. Morandé, Department of Psychiatry of the Niño Jesús Hospital, for providing us with the anorexic patients and the students of Ntra. Sra. de las Maravillas School and Nursing School of the Fundación Jiménez Dı́az (Madrid) for their kind collaboration.

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