Two Years of Denosumab and Teriparatide Administration in Postmenopausal Women With Osteoporosis (The DATA Extension Study): A Randomized Controlled Trial

Leder, Benjamin Z.; Tsai, Jui‐Hsiu; Uihlein, Alexander V.; Burnett-Bowie, Sherri-Ann M.; Zhu, Yuli; Foley, Katelyn; Lee, Hang; Neer, Robert M.

doi:10.1210/jc.2013-4440

Cited by 237 publications

(173 citation statements)

References 24 publications

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“…One hundred postmenopausal women with osteoporosis were randomized to receive teriparatide and denosumab, alone or in combination for 12 months. This study showed a densitometric bene fit in year 1 in the combination arm which was sustained in year 2 (43). As anticipated, patients on monotherapy with denosumab showed a decrease in BTMs while patients in the teriparatide alone arm showed an increase of BTMs.…”

Section: Pthsupporting

confidence: 79%

Bone markers and osteoporosis therapy

Bandeira

Costa

Filho

et al. 2014

Arq Bras Endocrinol Metab

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Several factors are involved in determining bone quality including bone density, bone turnover, the extent of trabecular bone connectivity, cortical porosity and geometry. Metabolically active and in a continuous process of remodeling, approximately 20% of bone tissue is renewed annually. Bone turn over markers (BTM) are frequently used in clinical trials and to provide valid information about the effectiveness of osteoporosis treatment, reflecting the state of bone metabolism and its response to treatment, although they are not useful alone to estimate bone loss. In this review the behavior of BTM from different clinical trials or different osteoporotic drugs will be addressed. Arq Bras Endocrinol Metab. 2014;58(5):504-13 Keywords Bone markers; osteoporosis; bone density ReSumoDiversos fatores estão envolvidos na determinação da qualidade óssea, incluindo a densidade óssea, a remodelação óssea, a extensão da conectividade do osso trabecular, porosidade cortical e geometria. Metabolicamente ativo e, em um processo contínuo de remodelação, cerca de 20% do tecido ósseo é renovado anualmente. Por sua vez, marcadores de turnover ósseo (BTM) são frequentemente utilizados em estudos clínicos e fornecem informações válidas sobre a eficácia do tratamento da osteoporose, o que reflete o metabolismo ósseo e sua resposta ao tratamento, embora eles não sejam úteis somente para estimar a perda óssea. Nesta revisão, o comportamento dos BTM em ensaios clínicos diferentes e com diferentes drogas osteoporóticas será abordado. one is a specific type of tissue composed primarily of type I collagen impregnated with minerals in the form of hydroxyapatite crystals. Several factors are involved in determining bone quality including bone density, bone turnover, the extent of trabecular bone connectivity, cortical porosity and geometry (Figure 1) (1). Metabolically active and in a continuous process of remodeling, approximately 20% of bone tissue is renewed annually (2). This complex process begins at birth and is maintained throughout life. The active cellular participants in this process, often configured as multiple multicellular units, are osteoclasts, osteoblasts and osteocytes.The system is highly regulated by many factors. For example, osteoprotegerin (OPG) (osteoprotegerin), receptor activator of NF-kappaB (RANK) and its cognate ligand, (RANKL), form a metabolic regulatory system focused upon bone resorption (3). Additionally there are other factors that influence bone turnover, such as parathyroid hormone (PTH), 1,25-dihydroxyvitamin D (calcitriol), prostaglandin E2 and interleukins (4). The process of bone turnover leads to the release of factors that give highly relevant information on rates of bone formation and resorption (Figure 2).

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Section: Pthsupporting

confidence: 79%

Bone markers and osteoporosis therapy

Bandeira

Costa

Filho

et al. 2014

Arq Bras Endocrinol Metab

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“…In patients on prior bisphosphonate, the increase at the total hip was not progressive as there was an early reduction in total hip BMD before the increase in the later months of treatment, particularly in those who were previously treated with alendronate or risedronate (14). Similar continued increases in BMD to 24 months have been reported in other studies (3,(15)(16)(17). Quantitative computed tomography allows the study of bone strength by applying finite element models.…”

supporting

confidence: 82%

“…Bone formation markers increase within days of starting teriparatide and reach a peak between 6 and 12 months. They remain above baseline for the whole of the 24 month treatment period (15,16). The markers even remain elevated in the setting of glucocorticoid-induced osteoporosis (3).…”

Section: Bone Turnover Markersmentioning

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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“…With the de novo combination of TPTD and denosumab, most of the TPTD-induced bone formation is likely to be modeling based because denosumab is such a potent resorption inhibitor, even when combined with TPTD. (47,48) With the de novo combination treatment, both spine and hip BMD increments were larger than observed with either agent alone, and high-resolution peripheral QCT indicated that the TPTD-induced increment in cortical porosity was reduced in the radius and tibia with combination therapy. (49) …”

Section: Cortical Bone Envelopementioning

confidence: 99%

Treatment Sequence Matters: Anabolic and Antiresorptive Therapy for Osteoporosis

Cosman

Nieves

Dempster

2016

Journal of Bone and Mineral Research

197

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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Two Years of Denosumab and Teriparatide Administration in Postmenopausal Women With Osteoporosis (The DATA Extension Study): A Randomized Controlled Trial

Cited by 237 publications

References 24 publications

Bone markers and osteoporosis therapy

Bone markers and osteoporosis therapy

Anabolic treatment for osteoporosis: teriparatide

Treatment Sequence Matters: Anabolic and Antiresorptive Therapy for Osteoporosis

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