Effects of teriparatide [rhPTH (1–34)] treatment on structural geometry of the proximal femur in elderly osteoporotic women

Uusi‐Rasi, Kirsti; Semanick, Lisa M.; Zanchetta, José R.; Bogado, César E.; Eriksen, Erik Fink; Sato, Masahiko; Beck, Thomas

doi:10.1016/j.bone.2005.03.003

Cited by 144 publications

(81 citation statements)

References 43 publications

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“…This may not translate into decreased mechanical strength, however, because the porosity is concentrated at the endocortical surface (close to the neutral axis of bone) and may be offset by increased periosteal apposition and increased cortical thickness. (36)(37)(38) Nevertheless, cotreatment with zoledronic acid may prevent the teriparatide-induced increase in cortical porosity, thus potentially strengthening the cortex and, as observed in this study, increasing hip BMD beyond values achieved with teriparatide alone. (39) The lack of continued increase in BMD at the hip during the latter 6 months in the combination group of our study may be due to increased cortical remodeling and resulting increases in cortical porosity as the effect of zoledronic acid wanes.…”

Section: Discussionmentioning

confidence: 53%

“…(4,8,9) In one head-to-head comparison of alendronate and teriparatide in patients with glucocorticoid-induced osteoporosis, vertebral fracture (but not nonvertebral fracture) incidence was lower with teriparatide than with alendronate. (10) At the hip, teriparatide increases areal BMD as assessed by dual-energy X-ray absorptiometry (DXA), (3) volumetric BMD as assessed by quantitative computed tomography (QCT), (11) cortical cross-sectional area (but not diameter) of the femoral neck (11,12) and hip strength as assessed by finiteelement modeling (9) and by hip structural analysis. (12) However, the pivotal teriparatide trial (3) was not powered adequately for hip fracture outcome (there were only 9 hip fractures), and the areal BMD effects of teriparatide at the hip as assessed by DXA are smaller than those seen in the spine (3) and not consistently greater than those of alendronate.…”

Section: Introductionmentioning

confidence: 99%

“…(10) At the hip, teriparatide increases areal BMD as assessed by dual-energy X-ray absorptiometry (DXA), (3) volumetric BMD as assessed by quantitative computed tomography (QCT), (11) cortical cross-sectional area (but not diameter) of the femoral neck (11,12) and hip strength as assessed by finiteelement modeling (9) and by hip structural analysis. (12) However, the pivotal teriparatide trial (3) was not powered adequately for hip fracture outcome (there were only 9 hip fractures), and the areal BMD effects of teriparatide at the hip as assessed by DXA are smaller than those seen in the spine (3) and not consistently greater than those of alendronate. (13,14) In contrast, the antifracture effects of once-yearly zoledronic acid at the hip over 3 years are well documented (41% reduced hip fracture risk in postmenopausal women with osteoporosis).…”

Section: Introductionmentioning

confidence: 99%

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Effects of intravenous zoledronic acid plus subcutaneous teriparatide [rhPTH(1–34)] in postmenopausal osteoporosis

Cosman

Eriksen

Recknor

et al. 2010

Journal of Bone and Mineral Research

303

172

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Clinical data suggest concomitant therapy with bisphosphonates and parathyroid hormone (PTH) may blunt the anabolic effect of PTH; rodent models suggest that infrequently administered bisphosphonates may interact differently. To evaluate the effects of combination therapy with an intravenous infusion of zoledronic acid 5 mg and daily subcutaneous recombinant human (rh)PTH(1-34) (teriparatide) 20 mg versus either agent alone on bone mineral density (BMD) and bone turnover markers, we conducted a 1-year multicenter, multinational, randomized, partial double-blinded, controlled trial. 412 postmenopausal women with osteoporosis (mean age 65 AE 9 years) were randomized to a single infusion of zoledronic acid 5 mg plus daily subcutaneous teriparatide 20 mg (n ¼ 137), zoledronic acid alone (n ¼ 137), or teriparatide alone (n ¼ 138). The primary endpoint was percentage increase in lumbar spine BMD (assessed by dual-energy X-ray absorptiometry [DXA]) at 52 weeks versus baseline. Secondary endpoints included change in BMD at the spine at earlier time points and at the total hip, trochanter, and femoral neck at all time points. At week 52, lumbar spine BMD had increased 7.5%, 7.0%, and 4.4% in the combination, teriparatide, and zoledronic acid groups, respectively ( p < .001 for combination and teriparatide versus zoledronic acid). In the combination group, spine BMD increased more rapidly than with either agent alone ( p < .001 versus both teriparatide and zoledronic acid at 13 and 26 weeks). Combination therapy increased total-hip BMD more than teriparatide alone at all times (all p < .01) and more than zoledronic acid at 13 weeks ( p < .05), with final 52-week increments of 2.3%, 1.1%, and 2.2% in the combination, teriparatide, and zoledronic acid groups, respectively. With combination therapy, bone formation (assessed by serum N-terminal propeptide of type I collagen [PINP]) increased from 0 to 4 weeks, declined minimally from 4 to 8 weeks, and then rose throughout the trial, with levels above baseline from 6 to 12 months. Bone resorption (assessed by serum b-C-telopeptide of type I collagen [b-CTX]) was markedly reduced with combination therapy from 0 to 8 weeks (a reduction of similar magnitude to that seen with zoledronic acid alone), followed by a gradual increase after week 8, with levels remaining above baseline for the latter half of the year. Levels for both markers were significantly lower with combination therapy versus teriparatide alone ( p < .002). Limitations of the study included its short duration, lack of endpoints beyond DXA-based BMD (e.g., quantitative computed tomography and finite-element modeling for bone strength), lack of teriparatide placebo, and insufficient power for fracture outcomes. We conclude that while teriparatide increases spine BMD more than zoledronic acid and zoledronic acid increases hip BMD more than teriparatide, combination therapy provides the largest, most rapid increments when both spine and hip sites are considered. ß

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Section: Discussionmentioning

confidence: 53%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Effects of intravenous zoledronic acid plus subcutaneous teriparatide [rhPTH(1–34)] in postmenopausal osteoporosis

Cosman

Eriksen

Recknor

et al. 2010

Journal of Bone and Mineral Research

303

172

View full text Add to dashboard Cite

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“…(39) In contrast, a study of subjects from the Fracture Prevention Trial using DXA hip structure analysis (HSA) showed only modest improvements at the femoral neck and intertrochanteric sites, with no change at the femoral shaft. (40) The present results imply that that changes in bone density at different skeletal sites do not relate in any simple manner to the changes in K i and suggest that large increases in bone formation rate may not necessarily translate into increases in bone density.…”

Section: Discussionmentioning

confidence: 54%

Differential effects of teriparatide on regional bone formation using 18F-fluoride positron emission tomography

Frost

Siddique

Blake

et al. 2010

Journal of Bone and Mineral Research

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Teriparatide increases skeletal mass, bone turnover markers, and bone strength, but local effects on bone tissue may vary between skeletal sites. We used positron emission tomography (PET) to study 18 F-fluoride plasma clearance (K i ) at the spine and standardized uptake values (SUVs) at the spine, pelvis, total hip, and femoral shaft in 18 postmenopausal women with osteoporosis. Subjects underwent a 1-hour dynamic scan of the lumbar spine and a 10-minute static scan of the pelvis and femurs at baseline and after 6 months of treatment with 20 mg/day teriparatide. Blood samples were taken to derive the arterial input function and lumbar spine K i values evaluated using a three-compartment model. SUVs were calculated for the spine, pelvis, total hip, and femoral shaft. After 6 months treatment with teriparatide, spine K i values increased by 24% (p ¼ .0003), while other model parameters were unchanged except for the fraction of tracer going to bone mineral (k 3 /[k 2 þ k 3 ]), which increased by 23% (p ¼ .0006). In contrast to K i , spine SUVs increased by only 3% (p ¼ .84). The discrepancy between changes in K i and SUVs was explained by a 20% decrease in 18 F À plasma concentration. SUVs increased by 37% at the femoral shaft (p ¼ .0019), 20% at the total hip (p ¼ .032), and 11% at the pelvis (p ¼ .070). Changes in bone turnover markers and BMD were consistent with previous trials. We conclude that the changes in bone formation rate during teriparatide treatment as measured by 18 F À PET differ at different skeletal sites, with larger increases in cortical bone than at trabecular sites. ß

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“…Animal studies indicate that changes in iliac crest bone biopsies after PTH treatment correlate with microstructure in both femoral neck and vertebrae [15]. In a prospective randomized multi-centre study, teriparatide has been shown to positively influence HSA parameters such as section modulus and cross-sectional area [44].…”

Section: Discussionmentioning

confidence: 99%

Variation in the PTH Gene, Hip Fracture, and Femoral Neck Geometry in Elderly Women

et al. 2010

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Running title: PTH gene and hip geometry 2(25) ABSTRACT Purpose: Parathyroid hormone (PTH) is a principal regulator of calcium homeostasis.Previously, we studied single nucleotide polymorphisms (SNPs) present in the major genes in the PTH pathway (PTH, PTHrP, PTHR1, PTHR2) in relation to bone mineral density (BMD) and fracture incidence. We found that haplotypes of the PTH gene were associated with fracture risk independent of BMD. In this present study, we evaluated the relationship between PTH haplotypes and femoral neck bone size. Methods:Hip structure analysis (HSA) and BMD of the femoral neck was assessed by DXA in elderly women from the Malmö Osteoporosis Prospective Risk Assessment (OPRA) study.Data on hip fracture, sustained as the result of low trauma after the age of 45 years, was also analysed. Haplotypes derived from six polymorphisms in the PTH locus were analysed in 750 women.

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Effects of teriparatide [rhPTH (1–34)] treatment on structural geometry of the proximal femur in elderly osteoporotic women

Cited by 144 publications

References 43 publications

Effects of intravenous zoledronic acid plus subcutaneous teriparatide [rhPTH(1–34)] in postmenopausal osteoporosis

Effects of intravenous zoledronic acid plus subcutaneous teriparatide [rhPTH(1–34)] in postmenopausal osteoporosis

Differential effects of teriparatide on regional bone formation using 18F-fluoride positron emission tomography

Variation in the PTH Gene, Hip Fracture, and Femoral Neck Geometry in Elderly Women

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