The effect of osteoporosis treatment on bone mass.

Over the last two decades there have been significant developments in the pharmacotherapy of osteoporosis. The therapeutic arsenal has expanded with monoclonal antibodies which have been developed based on discoveries of the molecular mechanisms underlying bone resorption and bone formation. Denosumab, the antibody binding RANKL, inhibits bone resorption, and romosozumab, the antibody binding sclerostin, inhibits bone resorption and stimulates bone formation as well. Both antibodies have shown potent anti-fracture efficacy in randomized clinical trials and this review will discuss the preclinical and clinical studies focusing on the effects on bone mass. After discontinuation of these antibodies, bone mineral density quickly returns to baseline and in the case of denosumab, discontinuation can not only induce rebound bone loss, but also the occurrence of vertebral fractures. Therefore, sequential antiresorptive therapy to maintain bone mass gains and anti-fracture efficacy is of utmost importance and will also be discussed in this review.

• Publication year

  2022

• Venue

  Best practice & research. Clinical endocrinology & metabolism

• Publication date

  2022-02-01

• Fields of study

  Medicine

• Identifiers
  DOI 10.1016/j.beem.2022.101623PMID 35219602
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Comparative Effect of Zoledronate at 6 Versus 18 Months Following Denosumab Discontinuation

  2021cited by this paper
• Osteoclasts recycle via osteomorphs during RANKL-stimulated bone resorption

  2021cited by this paper
• Safety of therapy with and withdrawal from denosumab in fibrous dysplasia and McCune‐Albright syndrome: an observational study

  2021cited by this paper
• The duration of denosumab treatment and the efficacy of zoledronate to preserve bone mineral density after its discontinuation.

  2021cited by this paper
• Ten‐Year Simulation of the Effects of Denosumab on Bone Remodeling in Human Biopsies

  2021cited by this paper
• Osteoclasts recycle via osteomorphs during RANKL-stimulated bone resorption

  2021cited by this paper
• Osteoporosis drugs for prevention of clinical fracture in white postmenopausal women: a network meta-analysis of survival data

  2020cited by this paper
• Fracture risk and management of discontinuation of denosumab therapy: a systematic review and position statement by ECTS.

  2020cited by this paper
• A single dose of zoledronate preserves bone mineral density for up to 2 years after a second course of romosozumab

  2020cited by this paper
• Clinical efficacy and safety of drug interventions for primary and secondary prevention of osteoporotic fractures in postmenopausal women: Network meta-analysis followed by factor and cluster analysis

  2020cited by this paper
• Treatment with Zoledronate Subsequent to Denosumab in Osteoporosis: a Randomized Trial

  2020cited by this paper
• Pamidronate: A model compound of the pharmacology of nitrogen-containing bisphosphonates; A Leiden historical perspective.

  2020cited by this paper
• Reduction of Cortical Bone Turnover and Erosion Depth After 2 and 3 Years of Denosumab: Iliac Bone Histomorphometry in the FREEDOM Trial

  2019cited by this paper
• Bone mineral density gains with a second 12-month course of romosozumab therapy following placebo or denosumab

  2019cited by this paper
• Sixty spontaneous vertebral fractures after denosumab discontinuation in 15 women with early-stage breast cancer under aromatase inhibitors

  2019cited by this paper
• Comparative efficacy of bone anabolic therapies in women with postmenopausal osteoporosis: A systematic review and network meta-analysis of randomized controlled trials.

  2019cited by this paper
• Zoledronate for the Prevention of Bone Loss in Women Discontinuing Denosumab Treatment. A Prospective 2‐Year Clinical Trial

  2019cited by this paper
• Changes in Dkk-1, sclerostin, and RANKL serum levels following discontinuation of long-term denosumab treatment in postmenopausal women.

  2019cited by this paper
• Acute hypercalcemia and excessive bone resorption following anti-RANKL withdrawal: Case report and brief literature review.

  2019cited by this paper
• Effects of teriparatide on hip and upper limb fractures in patients with osteoporosis: a systematic review and meta-analysis

  2019cited by this paper
• Effects of 24 Months of Treatment With Romosozumab Followed by 12 Months of Denosumab or Placebo in Postmenopausal Women With Low Bone Mineral Density: A Randomized, Double‐Blind, Phase 2, Parallel Group Study

  2018cited by this paper
• A Phase III Randomized Placebo-Controlled Trial to Evaluate Efficacy and Safety of Romosozumab in Men With Osteoporosis

  2018cited by this paper
• Romosozumab increases bone mineral density in postmenopausal Japanese women with osteoporosis: A phase 2 study.

  2017cited by this paper
• Effects of teriparatide and risedronate on new fractures in post-menopausal women with severe osteoporosis (VERO): a multicentre, double-blind, double-dummy, randomised controlled trial.

  2017cited by this paper
• Romosozumab (sclerostin monoclonal antibody) versus teriparatide in postmenopausal women with osteoporosis transitioning from oral bisphosphonate therapy: a randomised, open-label, phase 3 trial.

  2017cited by this paper
• BPS804 Anti‐Sclerostin Antibody in Adults With Moderate Osteogenesis Imperfecta: Results of a Randomized Phase 2a Trial

  2017cited by this paper
• Kinetic reconstruction reveals time-dependent effects of romosozumab on bone formation and osteoblast function in vertebral cancellous and cortical bone in cynomolgus monkeys.

  2017cited by this paper
• Romosozumab or Alendronate for Fracture Prevention in Women with Osteoporosis

  2017cited by this paper
• Observations following discontinuation of long-term denosumab therapy

  2017cited by this paper
• Efficacy of anti-sclerostin monoclonal antibody BPS804 in adult patients with hypophosphatasia

  2017cited by this paper
• Romosozumab Treatment Converts Trabecular Rods into Trabecular Plates in Male Cynomolgus Monkeys

  2017cited by this paper
• Romosozumab Improves Bone Mass and Strength While Maintaining Bone Quality in Ovariectomized Cynomolgus Monkeys

  2017cited by this paper
• 10 years of denosumab treatment in postmenopausal women with osteoporosis: results from the phase 3 randomised FREEDOM trial and open-label extension.

  2017cited by this paper
• Romosozumab Treatment in Postmenopausal Women with Osteoporosis.

  2016cited by this paper
• Postmenopausal osteoporosis

  2016cited by this paper
• Sustained Modeling‐Based Bone Formation During Adulthood in Cynomolgus Monkeys May Contribute to Continuous BMD Gains With Denosumab

  2015cited by this paper
• Denosumab and teriparatide transitions in postmenopausal osteoporosis (the DATA-Switch study): extension of a randomised controlled trial.

  2015cited by this paper
• The Effect of Discontinuing Treatment With Blosozumab: Follow‐up Results of a Phase 2 Randomized Clinical Trial in Postmenopausal Women With Low Bone Mineral Density

  2015cited by this paper
• A Randomized, Double‐Blind Phase 2 Clinical Trial of Blosozumab, a Sclerostin Antibody, in Postmenopausal Women with Low Bone Mineral Density

  2015cited by this paper
• Multiple doses of sclerostin antibody romosozumab in healthy men and postmenopausal women with low bone mass: A randomized, double‐blind, placebo‐controlled study

  2014cited by this paper
• Single‐ and Multiple‐Dose Randomized Studies of Blosozumab, a Monoclonal Antibody Against Sclerostin, in Healthy Postmenopausal Women

  2014cited by this paper
• Progressive increases in bone mass and bone strength in an ovariectomized rat model of osteoporosis after 26 weeks of treatment with a sclerostin antibody.

  2014cited by this paper
• Implications of Osteoblast-Osteoclast Interactions in the Management of Osteoporosis by Antiresorptive Agents Denosumab and Odanacatib

  2014cited by this paper
• Romosozumab in postmenopausal women with low bone mineral density

  2014cited by this paper
• Parathyroid Hormone (PTH)/PTH-related Peptide Type 1 Receptor (PPR) Signaling in Osteocytes Regulates Anabolic and Catabolic Skeletal Responses to PTH*

  2013cited by this paper
• Role of RANK ligand and denosumab, a targeted RANK ligand inhibitor, in bone health and osteoporosis: a review of preclinical and clinical data.

  2012cited by this paper
• Skeletal and extraskeletal actions of denosumab

  2012cited by this paper
• Effects of denosumab treatment and discontinuation on bone mineral density and bone turnover markers in postmenopausal women with low bone mass.

  2011cited by this paper
• Single‐dose, placebo‐controlled, randomized study of AMG 785, a sclerostin monoclonal antibody

  2011cited by this paper
• Denosumab, a fully human RANKL antibody, reduced bone turnover markers and increased trabecular and cortical bone mass, density, and strength in ovariectomized cynomolgus monkeys.

  2011cited by this paper
• Two doses of sclerostin antibody in cynomolgus monkeys increases bone formation, bone mineral density, and bone strength

  2010cited by this paper
• Inhibition of sclerostin by monoclonal antibody increases bone formation, bone mass, and bone strength in aged male rats

  2010cited by this paper
• Sclerostin Antibody Treatment Increases Bone Formation, Bone Mass, and Bone Strength in a Rat Model of Postmenopausal Osteoporosis

  2009cited by this paper
• Effects of teriparatide in postmenopausal women with osteoporosis on prior alendronate or raloxifene: differences between stopping and continuing the antiresorptive agent.

  2009cited by this paper
• Denosumab for prevention of fractures in postmenopausal women with osteoporosis.

  2009cited by this paper
• Receptor activator of nuclear factor kappaB ligand and osteoprotegerin regulation of bone remodeling in health and disease.

  2008cited by this paper
• Effects of Two Years of Daily Teriparatide Treatment on BMD in Postmenopausal Women With Severe Osteoporosis With and Without Prior Antiresorptive Treatment

  2008cited by this paper
• Effects of previous antiresorptive therapy on the bone mineral density response to two years of teriparatide treatment in postmenopausal women with osteoporosis.

  2008cited by this paper
• Targeted Deletion of the Sclerostin Gene in Mice Results in Increased Bone Formation and Bone Strength

  2008cited by this paper
• Early responsiveness of women with osteoporosis to teriparatide after therapy with alendronate or risedronate.

  2008cited by this paper
• Bisphosphonates: how do they work?

  2008cited by this paper
• Skeletal actions of intermittent parathyroid hormone: effects on bone remodelling and structure.

  2007cited by this paper
• Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis.

  2007cited by this paper
• SOST Is a Ligand for LRP5/LRP6 and a Wnt Signaling Inhibitor*

  2005cited by this paper
• Differential Effects of Teriparatide on BMD After Treatment With Raloxifene or Alendronate

  2004cited by this paper
• Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST).

  2001cited by this paper
• Bone dysplasia sclerosteosis results from loss of the SOST gene product, a novel cystine knot-containing protein.

  2001cited by this paper
• Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. Vertebral Efficacy With Risedronate Therapy (VERT) Study Group.

  1999cited by this paper
• osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification.

  1998cited by this paper
• Osteoprotegerin: a novel secreted protein involved in the regulation of bone density.

  1997cited by this paper
• Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Fracture Intervention Trial Research Group.

  1996cited by this paper
• Skeletal metabolism in patients with osteoporosis after discontinuation of long-term treatment with oral pamidronate.

  1995cited by this paper

• Osteoporosis After Menopause and After Drug Therapy: The Molecular Mechanism of Bone Loss and Its Treatment

  2026cites this paper
• Spatiotemporal Remodeling of Bone as a Reversibly Adaptive Biological Material in Djungarian Hamsters under Regulated Photoperiod Conditions.

  2026cites this paper
• Cnicin Regulates Bone Turnover Homeostasis in Rats with Ovariectomy-Induced Osteoporosis via RANKL/RANK/OPG Pathway

  2025cites this paper
• Current and emerging bone resorption inhibitors for the treatment of osteoporosis

  2025cites this paper
• Kidney stones and metabolic bone diseases not linked to parathyroid disfunction: a proposal for an integrated management.

  2025cites this paper
• Medication for bone loss in female patients with anorexia nervosa: a systematic review and management algorithm

  2025cites this paper
• Approach to the patient - Transitions in Osteoporosis Therapy.

  2025cites this paper
• Sclerostin as a new target of diabetes-induced osteoporosis

  2024cites this paper
• Liuwei Dihuang Pills Enhance Osteogenic Differentiation in MC3T3-E1 Cells through the Activation of the Wnt/β-Catenin Signaling Pathway

  2024cites this paper
• Denosumab and the Rebound Effect: Current Aspects of Osteoporosis Therapy (Review)

  2024cites this paper
• Development of Calcium Phosphate Cement Composed of Silica-Modified Hydroxyapatite, Cerium Oxide, and Silica as an Osteoporotic Bone Filler

  2024cites this paper
• Incident Vertebral Fractures During Romosozumab Treatment in a Patient With a Pathogenic LRP5 Variant

  2024cites this paper
• Combining PTH(1‐34) and mechanical loading has increased benefit to tibia bone mechanics in ovariectomised mice

  2023cites this paper
• Clinical Studies On Romosozumab: An Alternative For Individuals With A High Risk Of Osteoporotic Fractures: A Current Concepts Review (Part II)

  2023cites this paper
• A summary of the Malaysian Clinical Practice Guidelines on the management of postmenopausal osteoporosis, 2022

  2023cites this paper
• Targeting strategies for bone diseases: signaling pathways and clinical studies

  2023cites this paper
• Cost Effectiveness of Denosumab for Secondary Prevention of Osteoporotic Fractures Among Postmenopausal Women in China: An Individual-Level Simulation Analysis

  2023influential citation
• Calcitonin gene-related peptide is potential therapeutic target of osteoporosis

  2022cites this paper