title: Impact of bisphosphonate wash-out prior to teriparatide therapy in clinical practice.
abstract: Concurrent use of bisphosphonate therapy reduces the anabolic effect of teriparatide. Consequently, in clinical practice bisphosphonates are discontinued and teriparatide therapy held for a few months to allow bone turnover to increase. We aimed to evaluate the effect of prior bisphosphonate exposure and the effect of bisphosphonate wash-out on the treatment response to teriparatide. Thirty-nine patients with primary osteoporosis (mean age 63.6 +/- 14.0 years), including 26 patients previously treated with oral bisphosphonates (median duration 53 months) and 13 bisphosphonate-naïve patients were started on teriparatide (20 mug daily) and followed prospectively over 12 months. The primary study outcome was change in bone formation markers (PINP, bone ALP, osteocalcin). Secondary outcomes included changes in bone resorption (betaCTX) and 12-month changes in BMD. Markers of bone formation increased early during teriparatide therapy and were followed by an increase in betaCTX (p < 0.001). The magnitude of the increase in bone markers was comparable in both patient groups irrespective of prior bisphosphonate exposure; similarly, increases in BMD after 12 months were not significantly different between bisphosphonate-pretreated and bisphosphonate-naïve patients (lumbar spine 7.1 vs. 8.9%, p = 0.58; total hip 4.1 vs. 1.1%, p = 0.48). The response of teriparatide was not related to the duration of bisphosphonate wash-out (median duration 4.2 months). This study confirms that beneficial effects of teriparatide on intermediate bone endpoints can be translated into clinical practice with less constringent methodological circumstances than in RCTs. Furthermore, as bisphosphonate wash-out does not appear to influence the treatment effect, teriparatide therapy can be started immediately after ceasing bisphosphonate therapy and wash-out.
authors.affiliation: Division of Endocrinology, Diabetes and Clinical Nutrition, University Hospital Basel, Missionsstrasse 24, 4055 Basel, Switzerland.
authors.forename: Christina
authors.initials: C
authors.lastname: Keel
authors.forename: Marius E
authors.initials: ME
authors.lastname: Kraenzlin
authors.forename: Claude A
authors.initials: CA
authors.lastname: Kraenzlin
authors.forename: Beat
authors.initials: B
authors.lastname: Müller
authors.forename: Christian
authors.initials: C
authors.lastname: Meier
mesh_terms: D000368:Aged; D019386:Alendronate / Q000627:therapeutic use; D000469:Alkaline Phosphatase / Q000097:blood; D015415:Biomarkers / Q000097:blood; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001861:Bone Regeneration / Q000187:drug effects; D001862:Bone Resorption / Q000517:prevention & control; D024042:Collagen Type I / Q000097:blood; D004164:Diphosphonates / Q000627:therapeutic use*; D004347:Drug Interactions; D012968:Etidronic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000097:blood; D008297:Male; D008875:Middle Aged; D009928:Organ Specificity; D015675:Osteocalcin / Q000097:blood; D010024:Osteoporosis / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D010455:Peptides / Q000097:blood; D000068296:Risedronic Acid; D019379:Teriparatide / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors
chemical_list: D015415:Biomarkers; D050071:Bone Density Conservation Agents; D024042:Collagen Type I; D004164:Diphosphonates; D007527:Isoenzymes; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D015675:Osteocalcin; D019379:Teriparatide; D000469:Alkaline Phosphatase; D000068296:Risedronic Acid; D012968:Etidronic Acid; D019386:Alendronate