Targeting fundamental aging mechanisms to treat osteoporosis

ABSTRACT Introduction: Osteoporotic fractures represent a growing burden of mortality, morbidity and socioeconomic cost to health-care systems worldwide. Osteoporosis is a disease uniquely associated with aging, therefore, an understanding of the physiological mechanisms underpinning its development as we age may open new avenues for therapeutic exploitation. Novel treatments, as well as refinement of the current approaches, are vital in the effort to sustain healthy, independent patients across the lifespan. Areas covered: This review covers the anabolic and catabolic pathways seen in bone maintenance, highlighting how they are changed with age, leading to osteoporosis. It will also discuss how these changes may be targeted therapeutically, in the development of new therapies, and the refinement of those already in use. Expert opinion: New effective and safe treatments for osteoporosis are still needed. Bone anabolics seem to be the most appropriate therapeutic approach to osteoporosis in older persons. Considering that bone and muscle mass synchronically decline with aging thus predisposing older persons to falls and fractures, combined therapeutic approaches to osteosarcopenia with a dual anabolic effect on muscle and bone will be a major advance in the treatment of these devastating conditions in the future.

• Publication year

  2019

• Venue

  Expert opinion on therapeutic targets

• Publication date

  2019-12-02

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1080/14728222.2019.1702973PMID 31815563
• 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.

• The diagnostic role of fat in osteosarcopenia

  2019cited by this paper
• Osteoanabolic and dual action drugs.

  2019cited by this paper
• The Detrimental Effects of Kynurenine, a Tryptophan Metabolite, on Human Bone Metabolism.

  2019cited by this paper
• Treatment with an inhibitor of fatty acid synthase attenuates bone loss in ovariectomized mice.

  2019cited by this paper
• Effects of denosumab on bone metabolism and bone mineral density with anti-TNF inhibitors, tocilizumab, or abatacept in osteoporosis with rheumatoid arthritis

  2018cited by this paper
• Good, Bad, or Ugly: the Biological Roles of Bone Marrow Fat

  2018cited by this paper
• SpringerLink Header: Bone Marrow and Adipose Tissue

  2018cited by this paper
• Inhibiting Cellular Senescence: A New Therapeutic Paradigm for Age-Related Osteoporosis

  2018cited by this paper
• Phase Ib/II study of lacnotuzumab (MCS110) combined with spartalizumab (PDR001) in patients (pts) with advanced tumors.

  2018cited by this paper
• Circulating osteogenic precursor cells: Building bone from blood

  2018cited by this paper
• Coupling of bone resorption and formation by RANKL reverse signalling

  2018cited by this paper
• Advances in the discovery of cathepsin K inhibitors on bone resorption

  2018cited by this paper
• PTH and PTHR1 in osteocytes. New insights into old partners

  2017cited by this paper
• Kynurenine, a Tryptophan Metabolite That Accumulates With Age, Induces Bone Loss

  2017cited by this paper
• DNA damage and senescence in osteoprogenitors expressing Osx1 may cause their decrease with age

  2017cited by this paper
• TCF7L2 mediates the cellular and behavioral response to chronic lithium treatment in animal models

  2017cited by this paper
• Sclerostin induced tumor growth, bone metastasis and osteolysis in breast cancer

  2017cited by this paper
• Colony-stimulating factor 1 receptor (CSF1R) inhibitors in cancer therapy

  2017cited by this paper
• Age-related Changes in Bone Marrow Mesenchymal Stromal Cells

  2017cited by this paper
• Targeting cellular senescence prevents age-related bone loss in mice

  2017cited by this paper
• Aging alters bone-fat reciprocity by shifting in vivo mesenchymal precursor cell fate towards an adipogenic lineage.

  2016cited by this paper
• Characterization of Regulatory Extracellular Vesicles from Osteoclasts

  2016cited by this paper
• ROS, Cell Senescence, and Novel Molecular Mechanisms in Aging and Age-Related Diseases

  2016influential reference
• Bone modeling and remodeling: potential as therapeutic targets for the treatment of osteoporosis

  2016influential reference
• A bispecific antibody targeting sclerostin and DKK-1 promotes bone mass accrual and fracture repair

  2016cited by this paper
• Merck &Co. drops osteoporosis drug odanacatib

  2016cited by this paper
• Identification of Senescent Cells in the Bone Microenvironment

  2016cited by this paper
• Allogeneic Mesenchymal Stem Cell Therapy Promotes Osteoblastogenesis and Prevents Glucocorticoid‐Induced Osteoporosis

  2016cited by this paper
• The effect of 8 or 5 years of denosumab treatment in postmenopausal women with osteoporosis: results from the FREEDOM Extension study

  2015cited by this paper
• Odanacatib: a review of its potential in the management of osteoporosis in postmenopausal women

  2015cited by this paper
• Topical Application of Lithium Chloride on the Pulp Induces Dentin Regeneration

  2015cited by this paper
• The Kynurenine Pathway of Tryptophan Degradation is Activated During Osteoblastogenesis

  2015cited by this paper
• The Role of Estrogen Receptor in Bone Cells

  2015cited by this paper
• Parathyroid hormone: anabolic and catabolic actions on the skeleton.

  2015cited by this paper
• Mechanisms of palmitate-induced lipotoxicity in human osteoblasts.

  2014cited by this paper
• T Cell Costimulation Molecules CD80/86 Inhibit Osteoclast Differentiation by Inducing the IDO/Tryptophan Pathway

  2014cited by this paper
• Cellular senescence and the senescent secretory phenotype: therapeutic opportunities.

  2013cited by this paper
• Mechanisms of palmitate-induced cell death in human osteoblasts

  2013cited by this paper
• Selenium in Bone Health: Roles in Antioxidant Protection and Cell Proliferation

  2013cited by this paper
• Role of the nuclear envelope in the pathogenesis of age-related bone loss and osteoporosis.

  2012cited by this paper
• Increased type II collagen cleavage by cathepsin K and collagenase activities with aging and osteoarthritis in human articular cartilage

  2012cited by this paper
• In osteoporosis, differentiation of mesenchymal stem cells (MSCs) improves bone marrow adipogenesis.

  2012cited by this paper
• Antioxidants, like coenzyme Q10, selenite, and curcumin, inhibited osteoclast differentiation by suppressing reactive oxygen species generation.

  2012cited by this paper
• Five Years of Cenosumab Exposure in Women With Postmenopausal Osteoporosis: Results From the First Two Years of the FREEDOM Extension

  2011cited by this paper
• Bisphosphonate use and atypical fractures of the femoral shaft.

  2011cited by this paper
• Lrp5 functions in bone to regulate bone mass

  2011cited by this paper
• Effects of intermittent parathyroid hormone treatment on osteoprogenitor cells in postmenopausal women.

  2011cited by this paper
• The Effects of Excipients and Particle Engineering on the Biophysical Stability and Aerosol Performance of Parathyroid Hormone (1-34) Prepared as a Dry Powder for Inhalation

  2011cited by this paper
• Effects of denosumab on bone turnover markers in postmenopausal osteoporosis

  2011cited by this paper
• Of mice and men: divergent risks of teriparatide-induced osteosarcoma

  2010cited by this paper
• Resveratrol prevents RANKL-induced osteoclast differentiation of murine osteoclast progenitor RAW 264.7 cells through inhibition of ROS production.

  2010cited by this paper
• Effect of transdermal teriparatide administration on bone mineral density in postmenopausal women.

  2010cited by this paper
• Transgenic mice overexpressing secreted frizzled-related proteins (sFRP)4 under the control of serum amyloid P promoter exhibit low bone mass but did not result in disturbed phosphate homeostasis.

  2010cited by this paper
• Phospholipase C signaling via the parathyroid hormone (PTH)/PTH-related peptide receptor is essential for normal bone responses to PTH.

  2010cited by this paper
• Osteoporosis: impact on health and economics

  2010cited by this paper
• Association between circulating osteoprogenitor cell numbers and bone mineral density in postmenopausal osteoporosis

  2010cited by this paper
• Circulating mesenchymal stem cells with abnormal osteogenic differentiation in patients with osteoporosis.

  2009cited by this paper
• Lithium's effect on bone mineral density.

  2009cited by this paper
• Inhibition of glycogen synthase kinase-3beta attenuates glucocorticoid-induced bone loss.

  2009influential reference
• Overexpression of Secreted Frizzled-Related Protein 1 Inhibits Bone Formation and Attenuates Parathyroid Hormone Bone Anabolic Effects

  2009cited by this paper
• Designing the ideal selective estrogen receptor modulator-an achievable goal?

  2009cited by this paper
• Wnt inhibitory factor 1 is epigenetically silenced in human osteosarcoma, and targeted disruption accelerates osteosarcomagenesis in mice.

  2009cited by this paper
• Inhibition of fatty acid biosynthesis prevents adipocyte lipotoxicity on human osteoblasts in vitro

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

  2009cited by this paper
• Wnt/beta-catenin signaling: components, mechanisms, and diseases.

  2009cited by this paper
• Bone and fat connection in aging bone

  2008cited by this paper
• The discovery of odanacatib (MK-0822), a selective inhibitor of cathepsin K.

  2008cited by this paper
• Gene expression analysis of major lineage‐defining factors in human bone marrow cells: Effect of aging, gender, and age‐related disorders

  2008cited by this paper
• Bisphosphonates: mechanism of action and role in clinical practice.

  2008cited by this paper
• Cleavage of type II collagen by cathepsin K in human osteoarthritic cartilage.

  2008cited by this paper
• Dual effect of strontium ranelate: stimulation of osteoblast differentiation and inhibition of osteoclast formation and resorption in vitro.

  2008cited by this paper
• Estrogen protects bone by inducing Fas ligand in osteoblasts to regulate osteoclast survival

  2008cited by this paper
• Estrogen prevents bone loss via estrogen receptor alpha and induction of Fas ligand in osteoclasts.

  2007cited by this paper
• Osteoclasts prefer aged bone

  2007cited by this paper
• Estrogen Prevents Bone Loss via Estrogen Receptor α and Induction of Fas Ligand in Osteoclasts

  2007cited by this paper
• Wnt/beta-catenin signaling in development and disease.

  2006cited by this paper
• Systematic Review: Bisphosphonates and Osteonecrosis of the Jaws

  2006cited by this paper
• Narrative [corrected] review: bisphosphonates and osteonecrosis of the jaws.

  2006cited by this paper
• RANKL-RANK signaling in osteoclastogenesis and bone disease.

  2006cited by this paper
• Mechanisms of Disease: is osteoporosis the obesity of bone?

  2006cited by this paper
• Essential Role of β-Catenin in Postnatal Bone Acquisition*

  2005cited by this paper
• Lrp5-independent activation of Wnt signaling by lithium chloride increases bone formation and bone mass in mice.

  2005cited by this paper
• Aging Increases Stromal/Osteoblastic Cell‐Induced Osteoclastogenesis and Alters the Osteoclast Precursor Pool in the Mouse

  2005cited by this paper
• Reduced Relative Risk of Fractures Among Users of Lithium

  2005cited by this paper
• Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation.

  2005cited by this paper
• Estrogen and Testosterone Use Different Cellular Pathways to Inhibit Osteoclastogenesis and Bone Resorption

  2005cited by this paper
• Circulating osteoprotegerin and receptor activator of NF‐κB ligand system are associated with bone metabolism in middle‐aged males

  2005cited by this paper
• Essential role of beta-catenin in postnatal bone acquisition.

  2005cited by this paper
• Indoleamine 2,3-dioxygenase expression is restricted to fetal trophoblast giant cells during murine gestation and is maternal genome specific.

  2004cited by this paper
• Antibiotic use in relation to the risk of breast cancer

  2004cited by this paper
• Reactive oxygen species mediate RANK signaling in osteoclasts.

  2004cited by this paper
• Expression of RANKL and OPG Correlates With Age‐Related Bone Loss in Male C57BL/6 Mice

  2003cited by this paper
• Skeletal Changes in Rats Given Daily Subcutaneous Injections of Recombinant Human Parathyroid Hormone (1-34) for 2 Years and Relevance to Human Safety

  2002cited by this paper
• High bone density due to a mutation in LDL-receptor-related protein 5.

  2002cited by this paper
• The search for the ideal SERM

  2002cited by this paper
• High bone density due to a mutation in LDL-receptor-related protein 5.

  2002cited by this paper
• Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis.

  2001cited by this paper
• LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development.

  2001cited by this paper
• Bone resorption by osteoclasts.

  2000cited by this paper
• TNF-alpha induces osteoclastogenesis by direct stimulation of macrophages exposed to permissive levels of RANK ligand.

  2000cited by this paper

• Exploring the molecular intersections of osteoporosis and sarcopenia: An integrated bioinformatics and experimental validation.

  2026cites this paper
• The canonical Wnt pathway in osteoporosis: a scoping review of key compounds and proteins modulating Wnt-induced osteogenesis

  2025cites this paper
• Mechanistic Insights and Therapeutic Strategies in Osteoporosis: A Comprehensive Review

  2024cites this paper
• Circ_0027885 sponges miR-203-3p to regulate RUNX2 expression and alleviates osteoporosis progression

  2024cites this paper
• Bone Cells Metabolic Changes Induced by Ageing.

  2023cites this paper
• Comparative Analysis of Fat Composition in Marrow, Serum, and Muscle from Aging C57BL6 mice.

  2022cites this paper
• A clinician's guide to the management of geriatric musculoskeletal disease: Part 1 - Osteoporosis

  2021cites this paper
• Evaluation of Risk Factors for Primary Fracture in Elderly Patients with Osteoporosis

  2021cites this paper
• Alginate oligosaccharide alleviates senile osteoporosis via the RANKL–RANK pathway in D‐galactose‐induced C57BL/6J mice

  2021cites this paper
• Effect of kettlebell training on bone mineral density in two older adults with osteoporosis: a multiple-case study from the BELL trial

  2021influential citation
• Long non-coding RNA RP11-84C13.1 promotes osteogenic differentiation of bone mesenchymal stem cells and alleviates osteoporosis progression via the miR-23b-3p/RUNX2 axis

  2021cites this paper
• Association between genetic variants in oxidative stress-related genes and osteoporotic bone fracture. The Hortega Follow-up Study.

  2021cites this paper
• QiangGuYin Modulates the OPG/RANKL/RANK Pathway by Increasing Secretin Levels during Treatment of Primary Type I Osteoporosis

  2021cites this paper
• Molecular Basis of Bone Aging

  2020cites this paper
• 1,25(OH)2D3 ameliorates palmitate-induced lipotoxicity in human primary osteoblasts leading to improved viability and function.

  2020cites this paper
• Substituted benzothiophene and benzofuran derivatives as a novel class of bone morphogenetic Protein-2 upregulators: Synthesis, anti-osteoporosis efficacies in ovariectomized rats and a zebrafish model, and ADME properties.

  2020cites this paper