title: Combination teriparatide and raloxifene therapy for postmenopausal osteoporosis: results from a 6-month double-blind placebo-controlled trial.
abstract: We compared combination treatment with teriparatide plus raloxifene with teriparatide alone in women with postmenopausal osteoporosis in a 6-month double-blind, placebo-controlled trial that measured biochemical markers of bone turnover and BMD. Markers of bone formation and spine BMD increased similarly with teriparatide alone and combination therapy. However, combination therapy induced a significantly smaller increase in bone resorption versus teriparatide alone and significantly increased total hip BMD versus baseline.
  
  
  BACKGROUND
  The effects of combining two approved treatments for osteoporosis with different modes of action were examined by comparing teriparatide [rhPTH(1-34)] monotherapy with combination teriparatide and raloxifene therapy.
  
  
  METHODS
  A 6-month randomized, double-blind trial comparing teriparatide plus raloxifene (n = 69) versus teriparatide plus placebo (n = 68) was conducted in postmenopausal women with osteoporosis.
  
  
  RESULTS
  Bone formation (N-terminal propeptide of type 1 collagen [PINP]) increased similarly in both treatment groups. However, the increase in bone resorption (serum C-terminal telopeptide of type I collagen [CTx]) in the combination group was significantly smaller than in the teriparatide-alone group (p = 0.015). Lumbar spine BMD significantly increased 5.19 +/- 0.67% from baseline in the teriparatide-alone group. In the combination group, lumbar spine (6.19 +/- 0.65%), femoral neck (2.23 +/- 0.64%), and total hip (2.31 +/- 0.56%) BMD significantly increased from baseline to study endpoint, and the increase in total hip BMD was significantly greater than in the teriparatide-alone group (p = 0.04). In the teriparatide-alone group, mean serum calcium levels increased from baseline to endpoint (0.30 +/- 0.06 mg/dl, p < 0.001), whereas mean serum phosphate remained unchanged. In the combination group, mean serum calcium was unchanged, and mean serum phosphate decreased (-0.20 +/- 0.06 mg/dl, p < 0.001) from baseline to endpoint. Changes in serum calcium (p < 0.001) and phosphate (p < 0.004) were significantly different between treatment groups. The safety profile of combination therapy was similar to teriparatide alone.
  
  
  CONCLUSIONS
  Combination therapy increased bone formation to a similar degree as teriparatide alone. However, the increase in bone resorption was significantly less and total hip BMD significantly increased for combination therapy compared with teriparatide alone. Combination treatment with raloxifene may thus enhance the bone forming effects of teriparatide. Further studies over longer treatment duration that include fracture endpoints are necessary to fully ascertain the clinical significance of combination raloxifene plus teriparatide therapy in postmenopausal osteoporosis.
authors.affiliation: Cleveland Clinic Foundation, Cleveland, Ohio, USA.
authors.forename: Chad
authors.initials: C
authors.lastname: Deal
authors.forename: Molly
authors.initials: M
authors.lastname: Omizo
authors.forename: Elliott N
authors.initials: EN
authors.lastname: Schwartz
authors.forename: Erik F
authors.initials: EF
authors.lastname: Eriksen
authors.forename: Per
authors.initials: P
authors.lastname: Cantor
authors.forename: Jingyuan
authors.initials: J
authors.lastname: Wang
authors.forename: Emmett V
authors.initials: EV
authors.lastname: Glass
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Myers
authors.forename: John H
authors.initials: JH
authors.lastname: Krege
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015519:Bone Density / Q000187:drug effects; D002118:Calcium / Q000097:blood / Q000652:urine; D003094:Collagen / Q000097:blood; D024042:Collagen Type I; D003401:Creatine / Q000652:urine; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007677:Kidney Function Tests; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy*; D010446:Peptide Fragments / Q000097:blood; D010455:Peptides / Q000097:blood; D010758:Phosphorus / Q000097:blood / Q000652:urine; D011347:Procollagen / Q000097:blood; D020849:Raloxifene Hydrochloride / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D019379:Teriparatide / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome; D014527:Uric Acid / Q000097:blood / Q000652:urine; D014839:Vomiting / Q000139:chemically induced
chemical_list: D024042:Collagen Type I; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; C052929:collagen type I trimeric cross-linked peptide; C047202:procollagen Type I N-terminal peptide; D019379:Teriparatide; D014527:Uric Acid; D010758:Phosphorus; D020849:Raloxifene Hydrochloride; D003094:Collagen; D003401:Creatine; D002118:Calcium