Repeated Serum Alkaline Phosphatase Measurements in the Treatment of Childhood Acute Bone and Joint Infections with High Doses of Antibiotics

Levels of serum alkaline phosphatase (ALP) and the hepatic enzyme ALT are used to monitor medication toxicity [1]. ALP is important in osteoarticular processes because, excluding the liver, the highest concentrations of this enzyme can be found in the bone [1, 2]. High doses of clindamycin and first-generation cephalosporins have cytotoxic effects against osteoblasts in vitro [3-5]. The serum concentration of bone-specific ALP reflects the cellular activity of osteoblasts, and ALP elevation is encountered during bone formation or increased bone turnover [2, 6]. Furthermore, high ALP concentrations are found under septic conditions [2, 6-8]. ALP values are age and gender specific and vary throughout infancy and puberty [6]. In our prospective trial in Finland during 1983-2005, we treated 265 patients (age range, 3 months to 15 years) who had acute bone and/or joint infection by using antibiotics at exceptionally high doses and sequentially measured ALP and ALT levels [3, 9-11]. Data collection has been described in previous reports [911]. Briefly, the participants were randomized to receive shortterm (20 days for osteomyelitis and 10 for septic arthritis) or long-term (30 days, regardless of manifestations) treatment with high-dose clindamycin (40 mg/kg/day divided into 4 equal doses, quater in die [four times a day, qid]) or a first-generation cephalosporin (150 mg/kg/day qid). The latter division was quasi-randomized. Intravenous administration lasted 2-4 days, and the course was completed orally with the same dosage. Children younger than 5 yr received adjuvant ampicillin or amoxicillin therapy (200 mg/kg/day qid) until Haemophilus influenzae type b (Hib) infection was ruled out [9]. Antibiotic-loaded cement and beads were not used. Staphylococcal infections were similarly treated, even if bacteremia was detected [12]. Only culture-positive cases were included in the main study. Children with known kidney or liver disease or with another underlying illness were excluded. Adjuvant dexamethasone therapy was not used, whereas non-steroidal anti-inflammatory drugs (NSAIDs) were given routinely [13]. Total ALP, ALT, and creatinine levels were measured sequentially from blood samples taken on days 1, 2, 10, 19, and 29. Measurements have been reported as the serum concentration in IU/L. Bone alkaline phosphatase (BAP) isoenzyme or the liver ALP isoenzyme were not independently separated and quantified. The ageand sex-specific reference values reported by Turan et al. [6] were used for ALP. For ALT levels of children younger than 18 months, our cut-off values were 60 and 55 U/L for boys and girls, respectively. For older children, the values were 40 and 35 U/L for boys and girls, respectively [14]. Statview (version 5.0.1, Abacus Corporation, Baltimore, MD, USA) was used for data analysis. A t-test was