Objective.Concerns exist that stimulant therapy of youths with attention-deficit/hyperactivity disorder (ADHD) may result in an increased risk for subsequent substance use disorders (SUD). We investigated all long-term studies in which pharmacologically treated and untreated youths with ADHD were examined for later SUD outcomes. Methods.A search of all available prospective and retrospective studies of children, adolescents, and adults with ADHD that had information relating childhood exposure to stimulant therapy and later SUD outcome in adolescence or adulthood was conducted through PubMed supplemented with data from scientific presentations. Meta-analysis was used to evaluate the relationship between stimulant therapy and subsequent SUD in youths with ADHD in general while addressing specifically differential effects on alcohol use disorders or drug use disorders and the potential effects of covariates. Results.Six studies—2 with follow-up in adolescence and 4 in young adulthood—were included and comprised 674 medicated subjects and 360 unmedicated subjects who were followed at least 4 years. The pooled estimate of the odds ratio indicated a 1.9-fold reduction in risk for SUD in youths who were treated with stimulants compared with youths who did not receive pharmacotherapy for ADHD (z = 2.1; 95% confidence interval for odds ratio [OR]: 1.1–3.6). We found similar reductions in risk for later drug and alcohol use disorders (z = 1.1). Studies that reported follow-up into adolescence showed a greater protective effect on the development of SUD (OR: 5.8) than studies that followed subjects into adulthood (OR: 1.4). Additional analyses showed that the results could not be accounted for by any single study or by publication bias. Conclusion.Our results suggest that stimulant therapy in childhood is associated with a reduction in the risk for subsequent drug and alcohol use disorders.

FGF-23 is a novel regulator of phosphate metabolism. We studied the regulation of FGF-23 by dietary phosphate in 66 men and women using two assays. Dietary phosphate restriction decreased FGF-23 and loading increased FGF-23 significantly. An assay that measured intact FGF-23 showed the effects of dietary phosphate much more clearly than an assay that also measures presumed biologically inactive fragments. Dietary phosphate is a key regulator of circulating FGF-23; choice of assay is critical when studying FGF-23 physiology.Introduction: Fibroblast growth factor 23 (FGF-23) is a novel phosphaturic factor discovered through genetic studies of patients with renal phosphate wasting disorders. Ablation of the FGF-23 gene in mice reduces renal phosphate excretion and increases serum phosphate, suggesting that FGF-23 is critical for normal phosphate homeostasis. We examined the role of dietary phosphate in the regulation of FGF-23 in humans. Materials and Methods: Sixty-six healthy males and females were randomized to either phosphate-depleted or -loaded diets for 5 days, after a 4-day run-in diet. FGF-23 was measured using an "intact" assay that only detects intact FGF-23 peptide and with a "C-terminal" assay that measures both intact FGF-23 peptide and presumed biologically inactive carboxyl terminal fragments. The main outcome was the within group change in FGF-23 with either phosphate depletion or loading. Results: Using the intact FGF-23 assay, mean FGF-23 area under the curve (AUC) decreased by 9 ± 16% with phosphate depletion (p ‫ס‬ 0.0041) and increased by 35 ± 29% with loading (p < 0.0001). Using the C-terminal FGF-23 assay, mean FGF-23 AUC decreased by 8 ± 12% with phosphate depletion (p ‫ס‬ 0.0003) and increased by 13 ± 20% with loading (p ‫ס‬ 0.0016). Increases in FGF-23 with phosphate loading were greater with the intact assay than with the C-terminal assay (p ‫ס‬ 0.0003). Using the intact assay only, FGF-23 was significantly associated with serum phosphate (r ‫ס‬ 0.39, p < 0.01), 24-h urinary phosphate (r ‫ס‬ 0.47, p < 0.01), fractional excretion of phosphate (r ‫ס‬ 0.29, p < 0.01), and 1,25-dihydroxyvitamin D (r ‫ס‬ −0.30, p < 0.01). The association between the assays was weak (r ‫ס‬ 0.26, p < 0.01). Conclusions: Dietary phosphate is a key regulator of circulating FGF-23 levels in humans. Additionally, choice of assay is critical when performing physiologic investigations of FGF-23.

Prednisone 5 mg/day suppresses multiple indices of bone formation in a randomized placebocontrolled trial in healthy postmenopausal females. This suggests that even low doses of prednisone may reduce bone repair or renewal and may have adverse effects on bone mass and/or bone strength.Introduction: High doses of chronic glucocorticoids are known to have adverse effects on bone, and measures to prevent bone loss are well established for doses >7.5 mg daily, because these doses can cause premature or exaggerated osteoporosis. However, it is unclear if chronic prednisone doses of 5 mg daily have the same effects on bone. There are no established recommendations for preventing glucocorticoid-induced osteoporosis in people taking prednisone 5 mg daily, a dose used frequently in medical practice to treat diseases of the lungs, joints, skin, muscles, eyes, nerves, etc. Our primary objective was to test whether prednisone 5 mg daily affects serum and urine indices of bone metabolism in healthy postmenopausal women. Our secondary objectives were to determine if prednisone 5 mg affected systolic or diastolic blood pressure or causes side effects. Materials and Methods: A double-blinded randomized placebo-controlled 8-week trial in 50 healthy postmenopausal women was conducted at the Massachusetts General Hospital Outpatient General Clinical Research Center. Patients were randomly assigned to prednisone 5 mg daily or matching placebo for 6 weeks, followed by a 2-week recovery phase. Markers of bone formation and resorption were determined at weeks 0, 2, 4, 6, and 8. Indices of osteoblast activity included serum propeptide of type I N-terminal procollagen (PINP), propeptide of type I C-terminal procollagen (PICP), osteocalcin, and bone-specific alkaline phosphatase (BSALP). Indices of osteoclast activity included urine and serum type I collagen N-telopeptide (NTX) and free urinary deoxypyridinoline (DPD). Results and Conclusions: Prednisone rapidly and significantly decreased serum PINP (p < 0.01), PICP (p < 0.01), and osteocalcin (p < 0.01) and free urinary deoxypyridinoline (p ‫ס‬ 0.017). These changes were largely reversed during the recovery period. Side effects were indistinguishable in the two groups. Neither systolic nor diastolic blood pressure changed significantly throughout the study between the two groups. In conclusion, low-dose prednisone significantly decreases indices of bone formation and may decrease indices of bone resorption in postmenopausal women. Further studies are needed to assess the effects of low-dose prednisone on BMD and fracture risk.

Several reports have suggested an increased prevalence of osteopenia and osteoporosis in HIV-infected individuals. Vitamin D deficiency may be a risk factor for osteoporosis and bone fractures. We aimed to determine the prevalence of vitamin D insufficiency in an outpatient HIV clinic in Boston. We collected serum levels of 25-OH vitamin D and evaluated calcium and vitamin D intake in adult HIV-positive outpatients during the winter and spring of 2005. Fifty-seven subjects were enrolled. The prevalence of moderate (< or = 20 and>10 ng/ml) and severe (< or =10 ng/ml) 25-OH vitamin D deficiency was 36.8% and 10.5%, respectively. Lower vitamin D intake was significantly associated with severe 25-OH vitamin D deficiency (p=0.01). Lactose intolerance tended to be associated with severe vitamin D deficiency (p=0.08). Antiretroviral use and low daily calcium intake were significantly associated with elevated parathyroid hormone levels (p=0.01 and 0.03, respectively). Vitamin D deficiency was frequent in ambulatory HIV-positive patients. HIV-infected individuals living in areas with low exposure to ultraviolet light during winter may benefit from vitamin D supplementation.