Comparative efficacy of parathyroidectomy and active surveillance in patients with mild primary hyperparathyroidism: a systematic review and meta-analysis.

Counseling for patients with primary hyperparathyroidism (PHPT) and mild hypercalcemia without indications for surgical intervention requires accurate estimates of the potential benefits of parathyroidectomy. We aim to summarize the available evidence regarding the benefits of parathyroidectomy that patients with mild PHPT without indications for surgery experience compared to observation. We searched multiple databases from inception to August 2015. We included randomized controlled trials (RCT) and observational studies that evaluated changes in bone health, quality of life or neuropsychiatric symptoms, or in the risk of nephrolithiasis, cardiovascular events, or death between patients undergoing parathyroidectomy or active surveillance. Eight studies were eligible. Risk differences were not significant, in part due to lack of events (fractures, nephrolithiasis, cardiovascular events, or deaths). No significant differences were observed across measures of bone health, quality of life, and neuropsychiatric symptoms. A single RCT evaluating bone mineral density (BMD) changes at 5 years found a small statistically significant effect favoring parathyroidectomy. Patients with mild PHPT without indications for surgery experience a limited number of adverse consequences during short-term follow-up limiting our ability to estimate the benefit of surgery during this timeframe. This information is helpful as these patients consider surgery versus active surveillance. Long-term data is warranted to determine who benefits in the long run from surgical intervention and the extent to which this benefit affects outcomes that matter to patients.

Severe non-infective systemic inflammatory response syndrome, shock, and end-organ dysfunction after zoledronic acid administration in a child.

INTRODUCTION: Zoledronic acid is an intravenous bisphosphonate used to increase bone mineral density and reduce the risk of fractures. Its safety profile compares well with pamidronate in pediatric patients. We describe an acute, severe, life-threatening, inflammatory reaction in a child. METHODS: A 7-year-old boy with complex medical problems and chronic ventilator requirements was admitted to the pediatric intensive care unit (due to ventilator needs) for zoledronic acid infusion and subsequent monitoring. His history was significant for osteoporosis secondary to immobilization with multiple fractures since 2 years of age, hypoxic-ischemic encephalopathy, quadriplegic cerebral palsy, seizure disorder, ventilator dependence, and pulmonary hypertension. He had previously been treated with four cycles of pamidronate without adverse events. He received 0.013 mg/kg of zoledronic acid infused over 30 minutes. Beginning 3 hours after completion of the infusion, he developed progressive tachycardia, fever, hypotension requiring vasopressor infusion, and increasing oxygen requirements. Laboratory studies revealed leukopenia, thrombocytopenia, elevated C-reactive protein, abnormal coagulation profile, metabolic acidosis, and negative cultures. The following day, he developed moderate acute respiratory distress syndrome and pulmonary hemorrhage requiring higher ventilatory settings, and subsequently diarrhea and abdominal distension. Initial clinical resolution was noted from the third day onward, and he was discharged on the sixth day after zoledronate administration. RESULTS: Our pediatric patient demonstrated an acute, severe, life-threatening reaction to zoledronic acid requiring intensive cardiorespiratory support without an underlying pre-existing inflammatory disorder. CONCLUSION: Our case highlights the importance of careful monitoring of children following zoledronic acid therapy. We recommend inpatient observation after an initial infusion of zoledronic acid in medically complex children. Children and their parents should be thoroughly counseled on the potential risks of bisphosphonate treatment, which can sometimes be severe and life threatening.

Bone turnover markers in Paget's disease of the bone: A Systematic review and meta-analysis.

UNLABELLED: The aim of this systematic review and meta-analysis is to study the utility of the commonly used bone turnover markers in evaluating disease activity in patients with Paget's disease of bone before and after treatment with bisphosphonates. We found good correlation between the bone turnover marker concentrations and disease activity assessed by bone scintigraphy. INTRODUCTION: Paget's disease of bone is a common skeletal disorder of the elderly. Bone turnover marker concentrations are used for diagnosis and follow-up. We aimed to compare the available bone turnover markers and determine their utility in assessing disease activity when compared to quantitative bone scintigraphy. METHODS: We conducted a systematic review and meta-analysis searching MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus. We evaluated total alkaline phosphatase (total ALP), bone-specific alkaline phosphatase (bone ALP), procollagen type 1 amino-terminal propeptide (P1NP), serum, and urine C-terminal telopeptide (uCTx and sCTx, respectively), and urine N-terminal telopeptide (uNTx). The main outcome of interest was the correlation of disease activity with concentrations of bone turnover markers in Paget's disease patients before and after treatment with bisphosphonates. Correlation coefficients were pooled across studies using the random effects model. RESULTS: We included 17 observational studies and one trial reporting on 953 patients. Prior to treatment, all studied bone turnover markers had moderate to strong correlation with scintigraphic indices (correlation coefficients ranging from 0.58 to 0.80) with no statistically significant difference between the bone turnover markers overall (p = 0.08). P1NP, uNTx, and bone ALP tend to have higher correlation with scintigraphy. After starting treatment with bisphosphonate, there was moderate to strong correlation with disease activity with all markers except bone ALP (correlation coefficients ranging from 0.43 to 0.70). CONCLUSION: The findings of this meta-analysis suggest the Paget's disease activity is best monitored by following P1NP levels. However, total ALP, bone ALP, and uNTx are good alternatives as markers of disease activity in untreated patients. Total ALP and uNTx can be useful in following patients with Paget's disease after treatment if P1NP is not available. Clinicians, however, should take availability, cost, and the presence of liver disease into consideration when deciding which bone turnover marker is most appropriate when evaluating patients with Paget's disease.