No abstract

The usefulness of bone turnover markers in Gaucher disease is still unclear and their utility in monitoring the effects of enzyme replacement therapy (ERT) on bone metabolism has not yet been investigated exhaustively. Skeletal involvement seems to improve slowly during ERT, but only a few studies evaluating bone mineral density (BMD) changes during a long follow-up period have been reported. The aim of this study was to assess the efficacy of ERT on bone involvement in a group of 12 type I Gaucher disease (GD I) patients by monitoring biochemical indices of bone resorption/formation and BMD measured by dual energy x-ray absorptiometry (DEXA). Serum (calcium, phosphorus, bone alkaline phosphatase isoenzyme, carboxyterminal propeptide of type I procollagen (PICP), carboxyterminal telopeptide of type I collagen (ICTP), osteocalcin, intact parathyroid hormone) and urinary (calcium, phosphorus, hydroxyproline and free deoxypyridinoline) markers of bone metabolism and lumbar BMD were measured at baseline, after 6 and 12 months, and then every year for a mean ERT follow-up period of 4.5 years (range 4.4-6 years). Twelve healthy adult subjects matched for age and sex were tested as negative controls. A significant decrease of PICP was detected in the patient group at baseline (mean value 100.52 ng/ml vs 142.45 ng/ml, p = 0.017), while ICTP was remarkably higher: mean value 3.93 ng/ml vs 2.72 ng/ml, p = 0.004 (two-sided Student's t-test). No changes in bone formation indices were observed during the follow-up period, while urinary calcium excretion increased significantly from 0.065 to 0.191 mg/mg creatinine (p = 0.0014) (repeated measures ANOVA). A significant BMD improvement was also detected after an average ERT period of 4.5 years: Z-score increased from -0.81 to -0.56 (p = 0.005) (two-sided Student's t-test). These data evidenced the ineffectiveness of the biochemical markers used in monitoring ERT efficacy in GD I skeletal involvement, whereas DEXA was demonstrated to be a reliable method with which to follow up BMD improvement.

Bone involvement is one of the most disabling aspects of type I Gaucher disease and its pathophysiology is still not well understood. As an invasive procedure, bone biopsies are not appropriate in a large population study. The development of sensitive bone resorption and formation tests have allowed the authors to study bone metabolism in a noninvasive manner in a group of type 1 Gaucher patients. Ten type I Gaucher adult patients with mild-to-severe bone disease were evaluated. Bone mineral density and markers of bone formation (total alkaline phosphatase and isoenzymes, carboxyterminal propeptide of type I procollagen, osteocalcin) and resorption (carboxyterminal telopeptide of type I collagen, urinary hydroxyproline, free-deoxypyridinoline and calcium) were measured in patients and in a control group, matched for sex and age. In Gaucher patients, carboxyterminal propeptide of type I procollagen (PICP), a bone formation index, was significantly lower compared with normal subjects (mean 101.17 ng/ml vs 140.75 ng/ml, P = 0.038), and analysis of bone resorption indexes showed a significant increase (mean 4.24 ng/ml vs 2.87 ng/ml, P = 0.012) of serum carboxyterminal telopeptide of type I collagen (ICTP). No significant differences were observed in osteocalcin, alkaline phosphatase, and urinary hydroxyproline. Bone mineral density revealed osteopenia in six patients, with a mean Z-score of ?1.04. It was not possible to show a relationship between sex, splenectomy status, age, weight, spleen, and liver volume and bone density, expressed as a Z-score nor a correlation between Z score and severity of skeletal disease. Results have shown a predominance of the resorption phase in the bone metabolism of Gaucher patients. These markers could be useful in monitoring the effect of enzyme replacement therapy on Gaucher disease skeletal involvement.

No abstract