Animal experiments show a dramatic improvement in skeletal repair by teriparatide. We tested the hypothesis that recombinant teriparatide, at the 20 mg dose normally used for osteoporosis treatment or higher, would accelerate fracture repair in humans. Postmenopausal women (45 to 85 years of age) who had sustained a dorsally angulated distal radial fracture in need of closed reduction but no surgery were randomly assigned to 8 weeks of once-daily injections of placebo (n ¼ 34) or teriparatide 20 mg (n ¼ 34) or teriparatide 40 mg (n ¼ 34) within 10 days of fracture. Hypotheses were tested sequentially, beginning with the teriparatide 40 mg versus placebo comparison, using a gatekeeping strategy. The estimated median time from fracture to first radiographic evidence of complete cortical bridging in three of four cortices was 9.1, 7.4, and 8.8 weeks for placebo and teriparatide 20 mg and 40 mg, respectively (overall p ¼ .015). There was no significant difference between the teriparatide 40 mg versus placebo groups ( p ¼ .523). In post hoc analyses, there was no significant difference between teriparatide 40 mg versus 20 mg (p ¼ .053); however, the time to healing was shorter in teriparatide 20 mg than placebo ( p ¼ .006). The primary hypothesis that teriparatide 40 mg would shorten the time to cortical bridging was not supported. The shortened time to healing for teriparatide 20 mg compared with placebo still may suggest that fracture repair can be accelerated by teriparatide, but this result should be interpreted with caution and warrants further study. ß

Objective. To compare the bone anabolic drug teriparatide (20 g/day) with the antiresorptive drug alendronate (10 mg/day) for treating glucocorticoidinduced osteoporosis (OP).Methods. This was a 36-month, randomized, double-blind, controlled trial in 428 subjects with OP (ages 22-89 years) who had received >5 mg/day of prednisone equivalent for >3 months preceding screening. Measures included changes in lumbar spine and hip bone mineral density (BMD), changes in bone biomarkers, fracture incidence, and safety.Results. Increases in BMD from baseline were significantly greater in the teriparatide group than in the alendronate group, and at 36 months were 11.0% versus 5.3% for lumbar spine, 5.2% versus 2.7% for total hip, and 6.3% versus 3.4% for femoral neck (P < 0.001 for all). In the teriparatide group, median percent increases from baseline in N-terminal type I procollagen propeptide (PINP) and osteocalcin (OC) levels were significant from 1 to 36 months (P < 0.01), and increases in levels of C-terminal telopeptide of type I collagen (CTX) were significant from 1 to 6 months (P < 0.01). In the alendronate group, median percent decreases in PINP, OC, and CTX were significant by 6 months and remained below baseline through 36 months (P < 0.001). Fewer subjects had vertebral fractures in the teriparatide group than in the alendronate group (3 [1.7%] of 173 versus 13 [7.7%] of 169; P ‫؍‬ 0.007), with most occurring during the first 18 months. There was no significant difference between groups in the incidence of nonvertebral fractures (16 [7.5%] of 214 subjects taking teriparatide versus 15 [7.0%] of 214 subjects taking alendronate; P ‫؍‬ 0.843). More subjects in the teriparatide group (21%) versus the alendronate group (7%) had elevated predose serum calcium concentrations (P < 0.001).Conclusion. Our findings indicate that subjects with glucocorticoid-induced OP treated with teriparatide for 36 months had greater increases in BMD and fewer new vertebral fractures than subjects treated with alendronate.Glucocorticoids are beneficial for treating chronic inflammatory conditions, such as rheumatoid ClinicalTrials.gov identifier: NCT00051558.

Hip fractures are common, morbid, costly, and associated with subsequent fractures. Historically, postfracture osteoporosis medication use rates have been poor, but have not been recently examined in a large-scale study. We conducted a retrospective, observational cohort study based on U.S. administrative insurance claims data for beneficiaries with commercial or Medicare supplemental health insurance. Eligible participants were hospitalized for hip fracture between January 1, 2002, and December 31, 2011, and aged 50 years or older at admission. The outcome of interest was osteoporosis medication use within 12 months after discharge. Patients were censored after 12 months, loss to follow-up, or a medical claim for cancer or Paget's disease, whichever event occurred first. During the study period, 96,887 beneficiaries met the inclusion criteria; they had a mean age of 80 years and 70% were female. A total of 34,389 (35.5%) patients were censored before reaching 12 months of follow-up. The Kaplan-Meier estimated probability of osteoporosis medication use within 12 months after discharge was 28.5%. The rates declined significantly from 40.2% in 2002, to 20.5% in 2011 (p for trend <0.001). In multivariable Cox proportional hazards models, a number of patient characteristics were associated with reduced likelihood of osteoporosis medication use, including older age and male gender. However, the predictor most strongly and most positively associated with osteoporosis medication use after fracture was osteoporosis medication use before the fracture (hazard ratio = 7.45; 95% confidence interval [CI], 7.23–7.69). Most patients suffering a hip fracture do not use osteoporosis medication in the subsequent year and treatment rates have worsened. © 2014 Eli Lilly and Company. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.

No abstract

Background There is a medical need for therapies that improve hip fracture healing. Teriparatide (Forteo 1 / Forsteo 1 , recombinant human parathyroid hormone) is a bone anabolic drug that is approved for treatment of osteoporosis and glucocorticoid-induced osteoporosis in men and postmenopausal women at high fracture risk. Preclinical and preliminary clinical data also suggest that teriparatide may enhance bone healing.Questions/purposes We wished to test the hypotheses that treatment with teriparatide versus placebo would improve femoral neck fracture healing after internal fixation as measured by (1) frequency of revision surgery, (2) radiographic fracture healing, and (3) other outcomes including pain control, gait speed, and safety. Methods We initiated two separate, but identically designed, clinical trials to meet FDA requirements to provide substantial evidence to support approval of a new indication. The two prospective, randomized double-blind, placebo-controlled Phase III studies were designed to evaluate the effect of subcutaneous teriparatide (20 lg/day) for 6 months versus placebo on fracture healing at 24 months. The trials were conducted concurrently with a planned enrollment of 1220 patients per trial. However, enrollment was stopped owing to very slow patient accrual, and an a priori decision was made to pool the results of those studies for statistical analyses before study completion; pooling was specified in both protocols. Randomization was stratified by fixation (sliding hip screw or multiple cancellous screws) and fracture type (displaced or nondisplaced). An independent Central Adjudication Committee reviewed revision surgical procedures and radiographs. A total of 159 patients were randomized in the two trials (81 placebo, 78 teriparatide). The combined program had very low power to detect the originally This study was sponsored by Eli Lilly and Company. The institutions of authors (MB, NG, RW) have received, during the study period, funding from Eli Lilly and Company. One author (MB), or a member of his or her immediate family, has or may receive payments or benefits, during the study period, an amount of less than USD 10,000 from Eli Lilly and Company. One or more of the authors (LJ, KS, RB, KDK, MRW, BM) are employees of Eli Lilly and Company, that provided funding for this study. One of the authors (QIA) was an employee of Eli Lilly and Company at the time of the study but he no longer is employed by them. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research 1 editors and board members are on file with the publication and can be viewed on request. Each author certifies that his or her institution approved the human protocol for this investigation, that all investigations were conducted in conformity with ethical principles of research, and that informed consent for participation in the study was obtained. This study was conducted at the authors' various institutions. Clinical Orthopaedics and Related Research ®A Publication of The ...