Differential effects of teriparatide on BMD after treatment with raloxifene or alendronate.
We investigated the effects of 18 months of treatment with teriparatide in patients previously treated with long-term antiresorptive therapy using bone turnover markers and bone densitometry. Previous raloxifene treatment allowed for teriparatide-induced early bone marker and BMD increases comparable with previously published results for treatment-näive patients. Conversely, previous alendronate treatment reduced the bone marker and BMD response.


BACKGROUND
Teriparatide [rhPTH(1-34)] has been shown to increase BMD and reduce the risk of fracture in postmenopausal women with osteoporosis. Our objective was to investigate the skeletal effects of 18 months of treatment with teriparatide in women whose osteoporosis was previously treated with either alendronate or raloxifene.


METHODS
Daily subcutaneous injections of 20 microg teriparatide were administered for 18 months to 59 postmenopausal women, 60-87 years of age, with BMD T-scores </= -2.0 who had previously received either alendronate (ALN) or raloxifene (RLX) therapy for 18-36 months. All patients received daily calcium (1000 mg) and vitamin D (400 IU) supplementation. The primary study outcome was change in lumbar spine BMD measured by DXA. Secondary outcomes included changes in bone turnover markers, total hip BMD, and safety.


RESULTS
Median baseline bone turnover marker levels in prior ALN patients were about one-half those of prior RLX patients. During teriparatide treatment, bone markers in prior ALN patients increased later and peaked at about one-third lower levels compared with prior RLX patients. During the first 6 months, there were statistically significant (p < 0.05) group differences in BMD change at the hip (prior ALN -1.8% versus prior RLX +0.5%) and at the spine (prior ALN +0.5% versus prior RLX +5.2%). The positive slopes in hip and lumbar spine BMD were similar in both groups between 6 and 18 months. After 18 months, mean lumbar spine BMD increased 10.2% in prior RLX compared with 4.1% in prior ALN (p < 0.05) patients. Furthermore, at 18 months, mean total hip BMD had significantly increased (1.8%, p < 0.05) in prior RLX patients but was not different from baseline in prior ALN patients.


CONCLUSIONS
Teriparatide treatment stimulates bone turnover in patients pretreated with both RLX and ALN. Prior treatment with RLX allows for the expected teriparatide-induced BMD increases comparable with those previously reported for treatment-näive patients. In contrast, prior treatment with ALN prevents increases in BMD, particularly in the first 6 months.
Ettinger
Bruce
B
Division of Research, Kaiser Permanente Medical Care Program, Oakland, California, USA. vmettinger@aol.com
San Martin
Javier
J
Crans
Gerald
G
Pavo
Imre
I
D000368:Aged; D000369:Aged, 80 and over; D019386:Alendronate / Q000627:therapeutic use*; D000469:Alkaline Phosphatase / Q000097:blood; D015415:Biomarkers / Q000097:blood; D015519:Bone Density / Q000187:drug effects*; D003094:Collagen / Q000097:blood; D024042:Collagen Type I; D004347:Drug Interactions; D005260:Female; D006615:Hip / Q000000981:diagnostic imaging; D006801:Humans; D008137:Longitudinal Studies; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging / Q000187:drug effects; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood; D015663:Osteoporosis, Postmenopausal / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D010281:Parathyroid Hormone / Q000097:blood; D010455:Peptides / Q000097:blood; D011859:Radiography; D020849:Raloxifene Hydrochloride / Q000627:therapeutic use*; D019379:Teriparatide / Q000627:therapeutic use*
D015415:Biomarkers; D024042:Collagen Type I; D010281:Parathyroid Hormone; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D015675:Osteocalcin; D019379:Teriparatide; D020849:Raloxifene Hydrochloride; D003094:Collagen; D000469:Alkaline Phosphatase; D019386:Alendronate