Teriparatide and osseous regeneration in the oral cavity

Abstract

Background: Intermittent administration of teriparatide, a drug composed of the first 34 amino acids of parathyroid hormone, has anabolic effects on bone. Although teriparatide has been evaluated for the treatment of osteoporosis and for the healing of fractures, clinical trials evaluating it for the treatment of osseous conditions of the oral cavity in humans are lacking.

Methods: A total of 40 patients with severe, chronic periodontitis underwent periodontal surgery and received daily injections of teriparatide (20 μg) or placebo, along with oral calcium (1000 mg) and vitamin D (800 IU) supplementation, for 6 weeks. The patients were followed for 1 year. The primary outcome was a radiographic linear measurement of alveolar bone level. Secondary outcomes included clinical variables, bone turnover markers in serum and oral fluid, systemic bone mineral density, and quality of life.

Results: Radiographic linear resolution of osseous defects was significantly greater after teriparatide therapy than after placebo beginning at 6 months, with a mean linear gain in bone at 1 year of 29% as compared with 3% (P<0.001). Clinical improvement was greater in patients taking teriparatide than in those taking placebo, with a reduction in periodontal probing depth of 33% versus 20% (2.42 mm vs. 1.32 mm) and a gain in clinical attachment level of 22% versus 7% (1.58 mm vs. 0.42 mm) in target lesions at 1 year (P = 0.02 for both comparisons). No serious adverse events were reported; however, the number of patients in the study was small. No significant differences were noted with respect to the other variables that were assessed.

Conclusions: Teriparatide, as compared with placebo, was associated with improved clinical outcomes, greater resolution of alveolar bone defects, and accelerated osseous wound healing in the oral cavity. Teriparatide may offer therapeutic potential for localized bone defects in the jaw. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT00277706 .).

Figure 1. Study Design

The timeline of events for the study is shown in Panel A. All patients received nonsurgical therapy (scaling and root planing) at least 4 weeks before surgery. Teriparatide or placebo was administered daily, along with 1000 mg of calcium and 800 IU of vitamin D daily, for 6 weeks beginning 3 days before surgery. Patients were evaluated over the course of 12 months after surgery. Serum refers to the collection of serum for assay; maintenance refers to a periodontal maintenance procedure that included supragingival and subgingival scaling and polishing. Screening, randomization, and follow-up of patients through the end of the study period are shown in Panel B. Only one patient (in the teriparatide group) was lost to follow-up at 12 months. In addition, another patient in the teriparatide group missed the 9-month visit, although she completed the study. DXA denotes dual-energy x-ray absorptiometry, and OHIP Oral Health Impact Profile quality-of-life survey.

Figure 2. Changes in Serum Biomarkers over Time

Mean levels of serum calcium (Panel A), 25-hydroxyvitamin D (Panel B), and bone-specific alkaline phosphatase (Panel C) are shown for the teriparatide and placebo groups at baseline, 6 weeks, and 6 months. All patients received vitamin D and calcium supplementation for a 6-week period, beginning 3 days before periodontal surgery. Levels of 25-hydroxyvitamin D were significantly higher than baseline levels in the placebo group at 6 weeks (P = 0.02). At 6 weeks, patients in the teriparatide group had a significantly greater increase from baseline in serum alkaline phosphatase levels than patients in the placebo group (P = 0.003). I bars indicate standard errors.

Figure 3. Changes in Radiographic and Clinical Variables over Time

Mean gains in linear bone, as measured radiographically with the use of standardized bitewing radiographs, are shown in Panel A. Patients in the teriparatide group had significantly greater resolution of defects than did patients in the placebo group beginning at 6 months, with maximum resolution of defects at 12 months (P = 0.03, P = 0.004, and P<0.001 for the comparisons at 6, 9, and 12 months, respectively). Panel B shows the mean reductions from baseline in probing depth; Panel C, the mean gains in clinical attachment level; and Panel D, the mean reductions in bleeding on probing. Reductions in probing depth were significantly greater in patients in the teriparatide group than in patients in the placebo group at 9 and 12 months (P = 0.02). Gains in the clinical attachment level were significantly greater in patients in the teriparatide group at 12 months (P = 0.02). There were no significant between-group differences with respect to bleeding on probing. I bars indicate standard errors.