Teriparatide and denosumab combination therapy and skeletal metabolism

Idolazzi, Luca; Rossini, Maurizio; Viapiana, Ombretta; Braga, V.; Fassio, Angelo; Benini, Camilla; Kunnathully, Vidya Satheesn; Adami, Silvano; Gatti, Davide

doi:10.1007/s00198-016-3647-y

Cited by 27 publications

(24 citation statements)

References 33 publications

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“…More specifically, the BMD changes for the combination, Dmab or TPTD monotherapy, respectively, were 12.9, 8.3 and 9.5% at the LS, 6.3, 3.2 and 2.0% at the TH, 6.8, 4.1 and 2.8% at the FN and 2.2, 2.1 and −1.7% at distal radius (110). Similar BMD trends at the LS and TH, although not statistically significant, were observed in another open-label study (111). The combination of TPTD and Dmab was also superior of either monotherapy in improving bone microarchitecture and estimated strength, especially in cortical bone (112).…”

Section: Combination Treatmentsupporting

confidence: 74%

THERAPY OF ENDOCRINE DISEASE: Denosumab vs bisphosphonates for the treatment of postmenopausal osteoporosis

Anastasilakis

Polyzos

Makras

2018

European Journal of Endocrinology

101

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The most widely used medications for the treatment of osteoporosis are currently bisphosphonates (BPs) and denosumab (Dmab). Both are antiresorptives, thus targeting the osteoclast and inhibiting bone resorption. Dmab achieves greater suppression of bone turnover and greater increases of bone mineral density (BMD) at all skeletal sites, both in naïve and pretreated patients. No superiority on fracture risk reduction has been documented so far. In long-term administration, BPs reach a plateau in BMD response after 2-3 years, especially at the hip, while BMD increases progressively for as long as Dmab is administered. Both BPs and Dmab are generally considered safe, although they have been correlated to rare adverse events, such as osteonecrosis of the jaw and atypical femoral fractures. Dmab should be preferred in patients with impaired renal function. BPs are embedded in the bone, from which they are slowly released during bone remodeling, therefore continuing to act for years after their discontinuation. In contrast, Dmab discontinuation fully and rapidly reverses its effects on bone markers and BMD and increases the risk for fractures; therefore, Dmab discontinuation should be discouraged, especially in previously treatment-naïve patients, regardless of the conventional fracture risk. In case of discontinuation, other treatment, mainly BPs, should immediately follow, although the optimal sequential treatment strategy is yet to be defined. Combination of teriparatide with Dmab or zoledronic acid, but not alendronate, provides increased BMD gains at all sites. In conclusion, both BPs and Dmab are safe and efficient therapeutic options although their particularities should be carefully considered in an individual basis.

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Section: Combination Treatmentsupporting

confidence: 74%

THERAPY OF ENDOCRINE DISEASE: Denosumab vs bisphosphonates for the treatment of postmenopausal osteoporosis

Anastasilakis

Polyzos

Makras

2018

European Journal of Endocrinology

101

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“…In the combination arm of the study, the increase in markers of bone formation was observed quite earlier than the increase in the ones of bone resorption. 67 This remark supported the hypothesis of a consequent wider anabolic window of the concurrent treatment than TPD alone. 67 The favorable metabolic profile of the combination therapy (DMAb plus TPD) found confirmation in the DATA-Switch study.…”

Section: Combination Therapysupporting

confidence: 61%

“…67 This remark supported the hypothesis of a consequent wider anabolic window of the concurrent treatment than TPD alone. 67 The favorable metabolic profile of the combination therapy (DMAb plus TPD) found confirmation in the DATA-Switch study. 68 This study compared the effects on BMD of three different therapeutic schemes: DMAb administered after TPD, TPD after DMAb, and the combination of the two medications given concurrently for 2 years, followed by DMAb alone.…”

Section: Combination Therapysupporting

confidence: 61%

“…65 Another small study compared the changes of bone turnover markers in patients treated with DMAb versus TPD versus a third therapeutic scheme: TPD added to ongoing DMAb (TPD was started 3 months after DMAb). 67 The results showed that the effects of TPD on bone turnover markers were not blunted by prior and concurrent DMAb administration. In the combination arm of the study, the increase in markers of bone formation was observed quite earlier than the increase in the ones of bone resorption.…”

Section: Combination Therapymentioning

confidence: 88%

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Pharmacological Management of Osteoporosis in Postmenopausal Women: The Current State of the Art

Gatti

Fassio

2019

jptcp

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Osteoporosis is a common disease that increases fracture risk. Fragility fractures bring heavy consequences in terms of mortality and disability, with burdensome health and social costs. In subjects with clinical bone fragility, the first goal is to identify the secondary forms of osteoporosis, especially in young subjects, in males and in patients who recently experienced a fragility fracture. In addition, before considering any sort of treatment, it is fundamental to check for adequate calcium and vitamin D intake, since their deficiency is the most common reason for drug failure. In the last decade of the 20th century, several molecules have been developed and proved to be effective in achieving the true goal of any antiosteoporotic drug: fracture prevention. In this article, we considered the most commonly prescribed antiresorptive drugs (hormonal therapy, bisphosphonates, and denosumab), the anabolic agents (teriparatide), the dual-action drugs (romosozumab), and the drugs characterized by an unclear mechanism of action (strontium ranelate) to provide physicians with useful insights for their clinical practice. We discussed the main criteria for the appropriate choice selection and management of each treatment. Finally, we addressed the current controversies related to treatment discontinuation, sequential, and combination therapy.

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“…Due to existing controversy concerning reference intervals of BTMs, for classification we used as cutoffs values recently proposed optimal treatment targets for anti-resorptive therapy. It worthy of mention in this connection that many, but not all 1 , 12 , studies suggested that P1NP and bCTX may provide information about both response to treatment and reduction of fracture risk following osteoporotic therapy with antiresorptive 7 , 23 , 24 , 26 , 48 , 51 , 52 or anabolic 6 , 53 - 59 agents. Almost all published studies demonstrated reduction in serum bCTX during antiresorptive therapy and rise in serum P1NP during therapy with teriparatide; these changes have been associated with an improvement in BMD and reduced fracture risk.…”

Section: Discussionmentioning

confidence: 99%

Bone Turnover Status: Classification Model and Clinical Implications

Fisher¹,

Fisher²,

Srikusalanukul³

et al. 2018

Int. J. Med. Sci.

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Aim: To develop a practical model for classification bone turnover status and evaluate its clinical usefulness.Methods: Our classification of bone turnover status is based on internationally recommended biomarkers of both bone formation (N-terminal propeptide of type1 procollagen, P1NP) and bone resorption (beta C-terminal cross-linked telopeptide of type I collagen, bCTX), using the cutoffs proposed as therapeutic targets. The relationships between turnover subtypes and clinical characteristic were assessed in1223 hospitalised orthogeriatric patients (846 women, 377 men; mean age 78.1±9.50 years): 451(36.9%) subjects with hip fracture (HF), 396(32.4%) with other non-vertebral (non-HF) fractures (HF) and 376 (30.7%) patients without fractures.Resalts: Six subtypes of bone turnover status were identified: 1 - normal turnover (P1NP>32 μg/L, bCTX≤0.250 μg/L and P1NP/bCTX>100.0[(median value]); 2- low bone formation (P1NP ≤32 μg/L), normal bone resorption (bCTX≤0.250 μg/L) and P1NP/bCTX>100.0 (subtype2A) or P1NP/bCTX<100.0 (subtype 2B); 3- low bone formation, high bone resorption (bCTX>0.250 μg/L) and P1NP/bCTX<100.0; 4- high bone turnover (both markers elevated ) and P1NP/bCTX>100.0 (subtype 4A) or P1NP/bCTX<100.0 (subtype 4B). Compared to subtypes 1 and 2A, subtype 2B was strongly associated with nonvertebral fractures (odds ratio [OR] 2.0), especially HF (OR 3.2), age>75 years and hyperparathyroidism. Hypoalbuminaemia and not using osteoporotic therapy were two independent indicators common for subtypes 3, 4A and 4B; these three subtypes were associated with in-hospital mortality. Subtype 3 was associated with fractures (OR 1.7, for HF OR 2.4), age>75 years, chronic heart failure (CHF), anaemia, and history of malignancy, and predicted post-operative myocardial injury, high inflammatory response and length of hospital stay (LOS) above10 days. Subtype 4A was associated with chronic kidney disease (CKD), anaemia, history of malignancy and walking aids use and predicted LOS>20 days, but was not discriminative for fractures. Subtype 4B was associated with fractures (OR 2.1, for HF OR 2.5), age>75 years, CKD and indicated risks of myocardial injury, high inflammatory response and LOS>10 days.Conclusions: We proposed a classification model of bone turnover status and demonstrated that in orthogeriatric patients altered subtypes are closely related to presence of nonvertebral fractures, comorbidities and poorer in-hospital outcomes. However, further research is needed to establish optimal cut points of various biomarkers and improve the classification model.

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Teriparatide and denosumab combination therapy and skeletal metabolism

Abstract: In this study, we showed that TPTD is able to express its biological activity even when bone turnover is fully suppressed by denosumab treatment. The combination therapy is associated with significant increases in both DKK1 and SOST.

Cited by 27 publications

References 33 publications

THERAPY OF ENDOCRINE DISEASE: Denosumab vs bisphosphonates for the treatment of postmenopausal osteoporosis

THERAPY OF ENDOCRINE DISEASE: Denosumab vs bisphosphonates for the treatment of postmenopausal osteoporosis

Pharmacological Management of Osteoporosis in Postmenopausal Women: The Current State of the Art

Bone Turnover Status: Classification Model and Clinical Implications

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