ReviewEndocrine reviews2017
Cathepsin K Inhibitors for Osteoporosis: Biology, Potential Clinical Utility, and Lessons Learned.
Review in Endocrine reviews, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 137 papers, 6 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
137 citing papers in PubMed, 6 syntheses or guidelines pooled it, 257 citations in OpenAlex.
- Effectiveness of anabolic and anti-resorptive agents for preventing postmenopausal osteoporosis fractures: a systematic review and network meta-analysis.Journal of orthopaedic surgery and research · 2025Pooled it
- Efficacy and safety of odanacatib for osteoporosis treatment: a systematic review and meta-analysis.Archives of osteoporosis · 2023Pooled it
- The Skeletal Effects of Tanshinones: A Review.Molecules (Basel, Switzerland) · 2021Pooled it
- Evaluating the cardiovascular safety of sclerostin inhibition using evidence from meta-analysis of clinical trials and human genetics.Science translational medicine · 2020Pooled it
- The Effect of Physical Activity on Bone Biomarkers in People With Osteoporosis: A Systematic Review.Frontiers in endocrinology · 2020Pooled it
- Osteomyelitis of the jaws in patients with pycnodysostosis: a systematic review.Brazilian journal of otorhinolaryngologyPooled it
- Potential targets and mechanisms of Di(2-ethylhexyl) phthalate exposure in inducing chronic kidney disease: a multimodal study integrating epidemiology, network toxicology, and Mendelian randomization.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Virtual Screening and Molecular Dynamics Simulations Identifying Natural Product-Derived Cathepsin K Inhibitors as Potential Therapeutics for Osteoporosis.International journal of molecular sciences · 2026Article
- Matrix Competence Failure in Osteoporosis: Mechanosensing, Osteoimmune Crosstalk, and Fragility Beyond Bone Mineral Density.Current medical science · 2026Review
- Proteolysis at the extracellular matrix interface: Molecular architects and regulators in health and disease.The FEBS journal · 2026Review
- Exercise-stimulated primary cilia on preosteoclasts promote periosteal-bone formation.Experimental & molecular medicine · 2026Article
- Heparan sulfate promotes autoactivation of procathepsin K by destabilizing the propeptide-catalytic domain interaction.The Biochemical journal · 2026Article
- Bone turnover marker rhythmicity: implications for osteoporosis treatment and fracture healing.Endocrine connections · 2026Review
- Macrophage polarization-related genes with potential causal roles in osteoporosis: a multi-omics Mendelian randomization study.Journal of orthopaedic surgery and research · 2026Article
- Cathepsins as Core Players in Obesity Pathogenesis: Emerging Therapeutic Targets.Biomolecules · 2026Review
- Pathophysiology and Molecular Signalling in Osteoporosis: Linking Risk Factors to Bone Loss.Journal of cellular and molecular medicine · 2026Review
- Crebanine protects against ovariectomy-induced bone loss by targeting Sirt1 to interfere with NF-κB acetylation and ROS activity.Journal of pharmaceutical analysis · 2026Article
- Article
- Therapeutic potency and the related mechanism of deinoxanthin in experimental animal and cell models of periodontitis.Scientific reports · 2026Article
- Relationship between cathepsin K and extracellular matrix dynamics: a comprehensive review.Frontiers in oncology · 2026Review
77 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Cathepsin K is a cysteine protease member of the cathepsin lysosomal protease family. Although cathepsin K is highly expressed in osteoclasts, lower levels of cathepsin K are also found in a variety of other tissues. Secretion of cathepsin K from the osteoclast into the sealed osteoclast-bone cell interface results in efficient degradation of type I collagen. The absence of cathepsin K activity in humans results in pycnodysostosis, characterized by increased bone mineral density and fractures. Pharmacologic cathepsin K inhibition leads to continuous increases in bone mineral density for ≤5 years of treatment and improves bone strength at the spine and hip. Compared with other antiresorptive agents, cathepsin K inhibition is nearly equally efficacious for reducing biochemical markers of bone resorption but comparatively less active for reducing bone formation markers. Despite multiple efforts to develop cathepsin K inhibitors, potential concerns related to off-target effects of the inhibitors against other cathepsins and cathepsin K inhibition at nonbone sites, including skin and perhaps cardiovascular and cerebrovascular sites, prolonged the regulatory approval process. A large multinational randomized, double-blind phase III study of odanacatib in postmenopausal women with osteoporosis was recently completed. Although that study demonstrated clinically relevant reductions in fractures at multiple sites, odanacatib was ultimately withdrawn from the regulatory approval process after it was found to be associated with an increased risk of cerebrovascular accidents. Nonetheless, the underlying biology and clinical effects of cathepsin K inhibition remain of considerable interest and could guide future therapeutic approaches for osteoporosis.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.