Bone Mineral Density Loss and Fracture Risk After Discontinuation of Anti-osteoporotic Drug Treatment: A Narrative Review

Elbers, Laura; Raterman, Hennie G.; Lems, Willem F.

doi:10.1007/s40265-021-01587-x

Cited by 26 publications

(17 citation statements)

References 31 publications

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“…It is not known whether discontinuation of the second, antiresorptive agent (usually a bisphosphonate, SERM or denosumab) induces the same effect as for the second drug used alone. In a recent narrative review of available clinical trials in which therapies were discontinued and followed up for a year or more, Elbers et al demonstrated 0.4% or lower decrease in femoral neck BMD after 1 year of discontinuation of therapy in both previously alendronate- and zoledronate-treated patients; hence in these patients a discontinuation of up to a year may be acceptable [ 108 ]. In the other reported agents (risedronate, ibandronate, raloxifene, teriparatide, denosumab and romosozumab) this percentage of bone loss at the femoral neck and total hip was at least 1%, with the largest decrease in BMD after discontinuation of denosumab and romosozumab, providing further support for the importance of continuation of antiresorptive agents after both agents [ 108 ].…”

Section: Long-term Treatment: Cycling Of Anabolic/antiresorptive Ther...mentioning

confidence: 99%

Management of patients at very high risk of osteoporotic fractures through sequential treatments

et al. 2022

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Osteoporosis care has evolved markedly over the last 50 years, such that there are now an established clinical definition, validated methods of fracture risk assessment and a range of effective pharmacological agents. Currently, bone-forming (anabolic) agents, in many countries, are used in those patients who have continued to lose bone mineral density (BMD), patients with multiple subsequent fractures or those who have fractured despite treatment with antiresorptive agents. However, head-to-head data suggest that anabolic agents have greater rapidity and efficacy for fracture risk reduction than do antiresorptive therapies. The European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) convened an expert working group to discuss the tools available to identify patients at high risk of fracture, review the evidence for the use of anabolic agents as the initial intervention in patients at highest risk of fracture and consider the sequence of therapy following their use. This position paper sets out the findings of the group and the consequent recommendations. The key conclusion is that the current evidence base supports an “anabolic first” approach in patients found to be at very high risk of fracture, followed by maintenance therapy using an antiresorptive agent, and with the subsequent need for antiosteoporosis therapy addressed over a lifetime horizon.

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Section: Long-term Treatment: Cycling Of Anabolic/antiresorptive Ther...mentioning

confidence: 99%

Management of patients at very high risk of osteoporotic fractures through sequential treatments

et al. 2022

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“…Osteoporosis is a common disease characterized by the disturbance of bone homeostasis, which mainly threatens the health of postmenopausal women and the elderly 1 . At present, the main treatment means are oral drugs to delay the progression of bone loss, but the effect is relatively limited 2,3 . As the pathogenesis of osteoporosis is little known, there is an absence of acceptable grounds for drug design.…”

Section: Introductionmentioning

confidence: 99%

RETRACTED: Trehalose improves palmitic acid‐induced apoptosis of osteoblasts by regulating SIRT3‐medicated autophagy via the AMPK/mTOR/ULK1 pathway

et al. 2022

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Accumulation of lipid substances decreased the activity of osteoblasts. Trehalose is a typical stress metabolite to form a protective membrane on cell surface which has been demonstrated to regulate lipid metabolism. This activity of Trehalose indicates the potential effect of osteoporosis treatment. Our study aimed to determine the therapeutic effect of Trehalose in high fat-induced osteoporosis. We used palmitic acid (PA) to mimic the state of high fat and observed the apoptosis ratio of osteoblasts increased. After adding Trehalose, the apoptosis ratio decreased obviously. Autophagy is a regulatory means involved in the process of apoptosis.We detected the autophagy protein and found that the expression of Beclin-1, Atg5, and LC3 II increased, and p62 decreased after Trehalose treatment. When adding an autophagy inhibitor (3-MA), the expression of Beclin-1, Atg5, and LC3 II decreased, and p62 increased. These results indicated autophagy was an important factor involved in the preventive effect of Trehalose in PA-induced apoptosis. SIRT3 is a mitochondrial gene that can inhibit apoptosis, which has been reported to promote autophagy. We used SIRT3-siRNA to silence the expression of SIRT3 and found the effect of Trehalose was counteracted. The apoptosis ratio increased and the expression of Beclin-1, Atg5, and LC3 II decreased, p62 increased. Additionally, we also fed the mice with a high-fat diet (HFD) and intragastrical Trehalose. The results showed that Trehalose could inhibit the bone mass loss with HFD. Our study revealed the effect and mechanism of Trehalose in the treatment of osteoporosis.

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“…Discontinuation of osteoporosis therapy is followed by a decline of BMD ( 51 ). This is especially problematic after discontinuation of long-term treatment with denosumab, which results in a rapid decreased in BMD, rise and overshoot of bone turnover markers, and increase of fracture risk ( 52 ).…”

Section: Discussionmentioning

confidence: 99%

Anabolic therapy for osteoporosis: update on efficacy and safety

Bandeira¹,

Lewiecki²

2022

Archives of Endocrinology and Metabolism

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Anabolic agents for the treatment of osteoporosis increase bone density, improve bone strength, and reduce fracture risk. They are distinguished from antiresorptive drugs by their property of increasing osteoblastic bone formation. Teriparatide and abaloparatide are parathyroid hormone receptor agonists that increase bone remodeling with bone formation increasing more than bone resorption. Romosozumab is a humanized monoclonal antibody to sclerostin that has a "dual effect" of increasing bone formation while decreasing bone resorption. The bone forming effects of anabolic therapy appear to be self-limited, making it imperative that it be followed by antiresorptive therapy to enhance or consolidate the beneficial effects achieved. Teriparatide, abaloparatide, and romosozumab each have unique pharmacological properties that must be appreciated when using them to treat patients at high risk for fracture. Clinical trials have shown a favorable balance of expected benefits and possible risks. Anabolic therapy is superior to bisphosphonates for high-risk patients, with greater benefit when initial treatment is with an anabolic agent followed by an antiresorptive drug, rather than the reverse sequence of therapy. Recent clinical practice guidelines have included recommendations with examples of patients who are candidates with anabolic therapy.

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Bone Mineral Density Loss and Fracture Risk After Discontinuation of Anti-osteoporotic Drug Treatment: A Narrative Review

Cited by 26 publications

References 31 publications

Management of patients at very high risk of osteoporotic fractures through sequential treatments

Management of patients at very high risk of osteoporotic fractures through sequential treatments

RETRACTED: Trehalose improves palmitic acid‐induced apoptosis of osteoblasts by regulating SIRT3‐medicated autophagy via the AMPK/mTOR/ULK1 pathway

Anabolic therapy for osteoporosis: update on efficacy and safety

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