Background. Adults with osteogenesis imperfecta (OI) have a high risk of fracture. Currently, few treatment options are available, and bone anabolic therapies have not been tested in clinical trials for OI treatment.Methods. 79 adults with OI were randomized to receive 20 μg recombinant human parathyroid hormone (teriparatide) or placebo for 18 months in a double-blind, placebo-controlled trial. The primary endpoint was the percent change in areal bone mineral density (aBMD) of the lumbar spine (LS), as determined by dualenergy X-ray absorptiometry. Secondary endpoints included percent change in bone remodeling markers and vertebral volumetric BMD (vBMD) by quantitative computed tomography, estimated vertebral strength by finite element analysis, and self-reported fractures.Results. Compared with the placebo group, the teriparatide group showed increased LS aBMD (6.1% ± 1.0% vs. 2.8% ± 1.0% change from baseline; P < 0.05) and total hip aBMD (2.6% ± 1.0% vs. -2.4% ± 1.0% change; P < 0.001). Vertebral vBMD and strength improved with teriparatide therapy (18% ± 6% and 15% ± 3% change, respectively), but declined with placebo (-5.0% ± 6% and -2.0% ± 3% change; P < 0.05 for both comparisons). Serum procollagen type 1 N-terminal propeptide (P1NP) and urine collagen N-telopeptide (NTx) levels increased with teriparatide therapy (135% ± 14% and 64% ± 10% change, respectively). Teriparatide-induced elevation of P1NP levels was less pronounced in severe forms of OI (type III/IV) compared with the milder form (type I). Type I OI patients exhibited robust BMD increases with teriparatide; however, there was no observed benefit for those with type III/IV OI. There was no difference in self-reported fractures between the 2 groups.Conclusions. Adults with OI, particularly those with less severe disease (type I), displayed a teriparatide-induced anabolic response, as well as increased hip and spine aBMD, vertebral vBMD, and estimated vertebral strength.Trial registration. Clinicaltrials.gov NCT00131469.

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Antineutrophil cytoplasmic antibodies (ANCA) are associated with vasculitis, including vasculitis induced by drugs such as the thionamides. The affected organ systems in thionamide-induced vasculitis have been primarily renal, musculoskeletal, and dermatologic. We describe the first case of thionamide-induced central nervous system vasculitis presenting as confusion, with complete resolution after discontinuation of propylthiouracil. We review the literature and summarize 42 additional cases of thionamide-induced ANCA-positive vasculitis since 1992. Propylthiouracil was responsible in 93% of cases and the predominant ANCA pattern on immunofluorescent staining was perinuclear (p-ANCA). Clinical improvement occurred after drug discontinuation in 93%, steroid therapy was used in some cases. The mean duration of treatment with thionamides was 35 months prior to presentation. Long-term medical treatment with thionamides for hyperthyroidism may increase the risk of this severe side effect.

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