Daily or Cyclical Teriparatide Treatment in Women With Osteoporosis on no Prior Therapy and Women on Alendronate

Cosman, Felicia; Nieves, Jeri W.; Zion, Marsha; Garrett, Patricia; Neubort, Simon; Dempster, David W.; Lindsay, Robert

doi:10.1210/jc.2015-1715

Cited by 33 publications

(56 citation statements)

References 21 publications

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“…(31,33) TPTD in treatment-naive postmenopausal women over 19 to 24 months increases hip BMD more than PTH, resulting in an average gain of about 3% in the TH and FN. (15,28,29,39) After TPTD, transition to a bisphosphonate leads to further increases of about 2% in both the TH and FN after 1 year. (32) After transition from TPTD to sequential denosumab, BMD increments in the TH and FN are even higher (about 6% in both sites after 1 year of denosumab).…”

Section: Effects Of Sequential Treatment On Hip Bmdmentioning

confidence: 99%

“…The situation is slightly different in individuals after transition from alendronate to TPTD where spine BMD does not increase as dramatically as in women who transition from TPTD to alendronate. (24)(25)(26)(27)(28)(29)(30)(31)(32)(33) However, this effect is minor compared with the effect of treatment sequence on BMD changes at the hip.…”

Section: Cortical Bone Envelopementioning

confidence: 99%

“…(18)(19)(20)(21)(22)(23) This is certainly true of TPTD and PTH. (24)(25)(26)(27)(28)(29)(30) BMD responses to initial TPTD/PTH followed by potent antiresorptive therapy are substantial in both spine and hip sites as a result of the effects of both components of the treatment sequence. (28,(31)(32)(33)(34) In contrast, several studies have indicated that hip BMD responses to TPTD are lower in patients who have already been pretreated with potent antiresorptive therapies and consistently decline transiently for the first year or even longer.…”

Section: Introductionmentioning

confidence: 99%

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Treatment Sequence Matters: Anabolic and Antiresorptive Therapy for Osteoporosis

Cosman

Nieves

Dempster

2016

Journal of Bone and Mineral Research

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203

129

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The effects of anabolic medications (teriparatide [TPTD] and parathyroid hormone [PTH]) differ in patients who have received recent treatment with potent antiresorptives. This perspective reviews studies evaluating bone density (BMD) and histomorphometric effects of treatment sequences beginning with TPTD/PTH followed by potent antiresorptives and those beginning with potent antiresorptives followed by switching to or adding TPTD. Effect of treatment sequence on spine BMD outcome is minor, with modest quantitative differences. However, when individuals established on potent bisphosphonates are switched to TPTD, hip BMD declines below baseline for at least the first 12 months after the switch to TPTD. This transient hip BMD loss is more prominent when the antiresorptive is denosumab; in this setting, hip BMD remains below baseline for almost a full 24 months. In a controlled comparison of those who switched from alendronate to TPTD versus those who added TPTD to ongoing alendronate, the effect on hip BMD was improved with combination therapy. Furthermore, hip strength improved with the addition of TPTD to ongoing alendronate, whereas it was neutral after switching from alendronate to TPTD, primarily due to the effect on cortical bone. Bone biopsy studies indicate that TPTD stimulates bone formation in patients who have not been treated previously as well as in patients on prior and ongoing bisphosphonates. Histomorphometric evidence suggests that use of alendronate with TPTD blocks the TPTD-induced increase in cortical porosity. When possible, we suggest anabolic therapy first, followed by potent antiresorptive therapy. The common practice of switching to TPTD only after patients have an inadequate response to antiresorptives (intercurrent fracture or inadequate BMD effect) is not the optimal utilization of anabolic treatment. In fact, this may result in transient loss of hip BMD and strength. In this setting, continuing a potent antiresorptive while starting TPTD might improve hip outcomes.

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Section: Effects Of Sequential Treatment On Hip Bmdmentioning

confidence: 99%

Section: Cortical Bone Envelopementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Treatment Sequence Matters: Anabolic and Antiresorptive Therapy for Osteoporosis

Cosman

Nieves

Dempster

2016

Journal of Bone and Mineral Research

Self Cite

203

129

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show abstract

“…Over 24 months, spine BMD increased 12.9% with denosumab and teriparatide, 9.5% with teriparatide alone and 8.3% with denosumab alone. In the cyclical study, women treated with cyclical teriparatide and alendronate had similar BMD gain to women treated with continuous teriparatide, despite only receiving half the dose of teriparatide (33). However, in other studies co-treatment with alendronate attenuated the BMD increase compared with teriparatide alone, so there may be some complexities in the interaction of alendronate and teriparatide (37,38).…”

Section: Combination Treatmentmentioning

confidence: 96%

“…They found that during the two-year period the anabolic effect assessed by bone turnover markers began to wane, as is usually observed and that there is very little biochemical response to a second period (Figure 2). Cosman treated patients with cyclical teriparatide -three months on and three months off -over 24 months and patients receiving this regime had significantly less BMD gain at 24 months compared with continuous daily treatment (33).…”

Section: What Is the Effect Of A Repeated Course Of Teriparatide?mentioning

confidence: 99%

Anabolic treatment for osteoporosis: teriparatide

Eastell

Walsh

2017

ccmbm

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SummaryTeriparatide is a safe and effective anabolic treatment for osteoporosis. In postmenopausal women, it increases BMD and decreases vertebral fractures by about 70% and non-vertebral fractures by about 45% (although there is no evidence that it prevents hip fractures). The current evidence indicates that it should be administered for a single course of 24 months, and followed with an anti-resorptive agent to maintain the BMD gain. There is no clear benefit to repeated or cyclical treatment. Combination treatment, particularly with denosumab achieves greater BMD increase than either agent alone, but there are no available fracture data for combination treatment. There are some unknowns; most fundamentally why daily PTH administration is anabolic to bone when continuous high PTH is catabolic. Also, a better understanding of why the anabolic action declines with time and why there is a poor response to repeated treatment may help us to use teriparatide more effectively, and increase our understanding of bone biology and osteoporosis pathophysiology.KEY WORDS: bone turnover markers; osteoporosis; bone formation; fracture; bone mineral density; teriparatide. IntroductionTeriparatide refers to the molecule that makes up the first 34 amino acids of the intact parathyroid hormone (PTH, 84 amino acids). When PTH is given continuously, it stimulates bone resorption and loss of trabecular bone, as seen in endogenous primary hyperparathyroidism. When it is given intermittently, such as by daily injections, then it is anabolic and increases trabecular bone. It not only increases trabecular connectivity but also cortical thickness, based on microcomputed tomography studies of iliac crest bone biopsies (1). Teriparatide is the only current licensed anabolic treatment for osteoporosis in many countries. In most regions, it is restricted to second-line use as osteoporosis treatment due to greater cost than first-line agents such as alendronate. There is now extensive clinical experience with teriparatide, a good evidence base for its safety and efficacy, and some data on sequential or combination use with other osteoporosis drugs. However, there are still several unknowns around its mechanism of action, and why its anabolic effect decreases with time and repeated treatment. Intact parathyroid hormone has been licenced in Europe, but it is no longer available and so will not be discussed further. Abaloparatide is a modified version of the N-terminal region of parathyroid hormone-related protein that is currently in development for the treatment of osteoporosis but is outside the scope of this article. IndicationsThe approved indications for treatment include the treatment of postmenopausal osteoporosis, male osteoporosis and glucocorticoid-induced osteoporosis. Teriparatide has been reported to improve bone mineral density in other clinical situations, such as osteogenesis imperfecta and anorexia nervosa, but it is not licenced for these indications, and so this is outside the scope of this article. We will focus on postmeno...

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Parathyroid Hormone and Abaloparatide Treatment for Osteoporosis

Cosman¹,

Greenspan²

2018

Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism

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Daily or Cyclical Teriparatide Treatment in Women With Osteoporosis on no Prior Therapy and Women on Alendronate

Abstract: Cyclic TPTD over 2 years improves BMD similarly to daily treatment in women who remain on ALN, despite only 50% of the TPTD dose. However, there does not appear to be a BMD advantage to cyclic administration in treatment-naive women for up to 24 months.

Cited by 33 publications

References 21 publications

Treatment Sequence Matters: Anabolic and Antiresorptive Therapy for Osteoporosis

Treatment Sequence Matters: Anabolic and Antiresorptive Therapy for Osteoporosis

Anabolic treatment for osteoporosis: teriparatide

Parathyroid Hormone and Abaloparatide Treatment for Osteoporosis

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