Cathepsin K Inhibitors for Osteoporosis: Biology, Potential Clinical Utility, and Lessons Learned

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Cathepsin K Inhibitors for Osteoporosis: Biology, Potential Clinical Utility, and Lessons Learned is …
instance of (P31):
review articleQ7318358
scholarly articleQ13442814

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P356DOI10.1210/ER.2015-1114
P932PMC publication ID5546879
P698PubMed publication ID28651365

P50authorSundeep KhoslaQ42164143
P2093author name stringMerry Jo Oursler
Matthew T Drake
Bart L Clarke
P2860cites workSuppression of bone formation by osteoclastic expression of semaphorin 4DQ24294299
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Coupling Signals between the Osteoclast and Osteoblast: How are Messages Transmitted between These Temporary Visitors to the Bone Surface?Q28083559
Structure and chromosomal assignment of the human cathepsin K geneQ28117956
Defects in TCIRG1 subunit of the vacuolar proton pump are responsible for a subset of human autosomal recessive osteopetrosisQ28140437
Mutations in the a3 subunit of the vacuolar H(+)-ATPase cause infantile malignant osteopetrosisQ28143618
Cancellous bone remodeling occurs in specialized compartments lined by cells expressing osteoblastic markersQ74488802
The collagenolytic activity of cathepsin K is unique among mammalian proteinasesQ77581104
Study of immunoelectron microscopic localization of cathepsin K in osteoclasts and other bone cells in the mouse femurQ77690449
Surgical outcomes after treatment of fractures in femur and tibia in pycnodysostosisQ79463027
High bone mineral density in pycnodysostotic patients with a novel mutation in the propeptide of cathepsin KQ79501815
Molecular analysis and characterization of nine novel CTSK mutations in twelve patients affected by pycnodysostosis. Mutation in brief #961. OnlineQ80068357
Mechanisms of the anabolic effects of teriparatide on bone: insight from the treatment of a patient with pycnodysostosisQ80779491
Impaired bone resorption in cathepsin K-deficient mice is partially compensated for by enhanced osteoclastogenesis and increased expression of other proteases via an increased RANKL/OPG ratioQ81304554
Mandibular osteomyelitis and fracture successfully treated with vascularised iliac bone graft in a patient with pycnodysostosisQ81399867
Odanacatib reduces bone turnover and increases bone mass in the lumbar spine of skeletally mature ovariectomized rhesus monkeysQ82663650
Safety and efficacy of the cathepsin K inhibitor ONO-5334 in postmenopausal osteoporosis: the OCEAN studyQ83396466
Odanacatib: location and timing are everythingQ83486054
Evaluation of high-resolution peripheral quantitative computed tomography, finite element analysis and biomechanical testing in a pre-clinical model of osteoporosis: a study with odanacatib treatment in the ovariectomized adult rhesus monkeyQ83794040
Morphea-like skin reactions in patients treated with the cathepsin K inhibitor balicatibQ84100615
An atypical subtrochanteric femoral fracture from pycnodysostosis: a lesson from natureQ84193438
Cathepsin K deficiency aggravates lung injury in hyperoxia-exposed newborn miceQ84487317
Odanacatib in the treatment of postmenopausal women with low bone mineral density: five years of continued therapy in a phase 2 studyQ84553314
Cathepsin K inhibitors prevent bone loss in estrogen-deficient rabbitsQ84795050
A case of osteosarcoma in a patient with pycnodysostosisQ84903999
A potential contribution of altered cathepsin L expression to the development of dermal fibrosis and vasculopathy in systemic sclerosisQ86897492
Bone turnover markers and pharmacokinetics of a new sustained-release formulation of the cathepsin K inhibitor, ONO-5334, in healthy post-menopausal womenQ87155621
Continuous treatment with odanacatib for up to 8 years in postmenopausal women with low bone mineral density: a phase 2 studyQ87296824
Effects of eight-month treatment with ONO-5334, a cathepsin K inhibitor, on bone metabolism, strength and microstructure in ovariectomized cynomolgus monkeysQ87786472
Coupling factors: how many candidates can there be?Q87860942
Osteoclast synthesis and secretion and activation of latent transforming growth factor betaQ72058811
Pycnodysostosis, with a familial chromosome anomalyQ72756749
Mineral density and bone strength are dissociated in long bones of rat osteopetrotic mutationsQ73069637
The osteoclast-associated protease cathepsin K is expressed in human breast carcinomaQ73931802
Cathepsin K gene mutations and 1q21 haplotypes in at patients with pycnodysostosis in an outbred populationQ73949564
'Eph'ective signaling: forward, reverse and crosstalkQ28179338
Loss of the ClC-7 chloride channel leads to osteopetrosis in mice and manQ28201425
Albers-Schönberg disease (autosomal dominant osteopetrosis, type II) results from mutations in the ClCN7 chloride channel geneQ28210464
Structure, expression, and regulation of the major noncollagenous matrix proteins of boneQ28247547
The regulation of cathepsin K gene expressionQ28251189
Increasing options for the treatment of osteoporosisQ28254516
Human cathepsin O2, a novel cysteine protease highly expressed in osteoclastomas and ovary molecular cloning, sequencing and tissue distributionQ28290432
The gene for pycnodysostosis maps to human chromosome 1cen–q21Q28296690
Localization of cathepsin K in human osteoclasts by in situ hybridization and immunohistochemistryQ28303355
Targeted disruption of the c-src proto-oncogene leads to osteopetrosis in miceQ29547898
A physical mechanism for coupling bone resorption and formation in adult human bone.Q30485638
Pycnodysostosis: clinical, radiologic, and endocrine evaluation and linear growth after growth hormone therapyQ31939946
Cathepsin K null mice show reduced adiposity during the rapid accumulation of fat storesQ33292685
Bone density, strength, and formation in adult cathepsin K (-/-) miceQ33374935
Osteoclasts control osteoblast chemotaxis via PDGF-BB/PDGF receptor beta signalingQ33379619
Cathepsin K analysis in a pycnodysostosis cohort: demographic, genotypic and phenotypic featuresQ33615956
Disruption of PTH receptor 1 in T cells protects against PTH-induced bone lossQ33680465
Characterization of novel cathepsin K mutations in the pro and mature polypeptide regions causing pycnodysostosis.Q33843319
T cells: critical bone regulators in health and diseaseQ34079698
Odanacatib treatment increases hip bone mass and cortical thickness by preserving endocortical bone formation and stimulating periosteal bone formation in the ovariectomized adult rhesus monkeyQ34082585
The molecular basis of osteoclast differentiation and activationQ34201145
Factors and mechanisms involved in the coupling from bone resorption to formation: how osteoclasts talk to osteoblastsQ34219161
OsteopetrosisQ34380528
Chemorepulsion by blood S1P regulates osteoclast precursor mobilization and bone remodeling in vivoQ34420830
Disruption of the cathepsin K gene reduces atherosclerosis progression and induces plaque fibrosis but accelerates macrophage foam cell formationQ34478046
Novel mutations of the cathepsin K gene in patients with pycnodysostosis and their characterizationQ34506716
Linking osteopetrosis and pycnodysostosis: regulation of cathepsin K expression by the microphthalmia transcription factor familyQ34514934
THE MALADY OF TOULOUSE-LAUTREC.Q34541226
Periosteal remodeling at the femoral neck in nonhuman primatesQ34543466
Novel pycnodysostosis mouse model uncovers cathepsin K function as a potential regulator of osteoclast apoptosis and senescenceQ34573852
Modulation of type beta transforming growth factor activity in bone cultures by osteotropic hormonesQ34610078
Near normalization of adult height and body proportions by growth hormone in pycnodysostosisQ34618386
Molecular and clinical analysis in a series of patients with Pyknodysostosis reveals some uncommon phenotypic findingsQ34769776
Effect of odanacatib on bone turnover markers, bone density and geometry of the spine and hip of ovariectomized monkeys: a head-to-head comparison with alendronateQ34786147
Coupling the activities of bone formation and resorption: a multitude of signals within the basic multicellular unitQ37506724
Cathepsin K knockout alleviates pressure overload-induced cardiac hypertrophyQ37593416
Cathepsin K in the immunohistochemical diagnosis of melanocytic lesionsQ37676779
Osteoclast Activity and Subtypes as a Function of Physiology and Pathology—Implications for Future Treatments of OsteoporosisQ37790176
Fracture management in pycnodysostosis: 27 years of follow-upQ37849733
Cysteine proteases: mode of action and role in epidermal differentiationQ38076304
Osteoclast-derived coupling factors in bone remodelingQ38108750
Atypical subtrochanteric and diaphyseal femoral fractures: second report of a task force of the American Society for Bone and Mineral ResearchQ38109833
Cysteine cathepsins and extracellular matrix degradation.Q38200374
Clinical and radiographic maxillofacial features of pycnodysostosisQ38206201
The reversal phase of the bone-remodeling cycle: cellular prerequisites for coupling resorption and formationQ38239680
The clinical spectrum and pathophysiology of skeletal complications in lysosomal storage disordersQ38490017
The effect of consanguinity on the reproductive wastage in the Turkish population.Q39283377
Afamin secreted from nonresorbing osteoclasts acts as a chemokine for preosteoblasts via the Akt-signaling pathwayQ39322224
A specific subtype of osteoclasts secretes factors inducing nodule formation by osteoblasts.Q39327208
Local regulators of skeletal growth: a perspectiveQ39498262
Normal and pathological remodeling of human trabecular bone: three dimensional reconstruction of the remodeling sequence in normals and in metabolic bone diseaseQ39748604
Upregulation of cathepsin S in psoriatic keratinocytesQ39784577
Treatment of osteoporoses by manipulation of coherent bone cell populationsQ39825655
Novel mutation and white matter involvement in an Indian child with pycnodysostosisQ40228038
Lysosomotropism of basic cathepsin K inhibitors contributes to increased cellular potencies against off-target cathepsins and reduced functional selectivityQ40348633
RANK ligand and interferon gamma differentially regulate cathepsin gene expression in pre-osteoclastic cells.Q40461557
Identification of cathepsin K as a novel marker of adiposity in white adipose tissue.Q40661967
Platelet-derived growth factor BB secreted from osteoclasts acts as an osteoblastogenesis inhibitory factorQ40754782
Overexpression of cathepsin K in mice decreases collagen deposition and lung resistance in response to bleomycin-induced pulmonary fibrosisQ41171992
Osteoprotection by semaphorin 3A.Q41791623
Pycnodysostosis with novel gene mutation and severe obstructive sleep apnoea: management of a complex caseQ41893850
Human cathepsin O2, a matrix protein-degrading cysteine protease expressed in osteoclasts. Functional expression of human cathepsin O2 in Spodoptera frugiperda and characterization of the enzymeQ42064898
A patient with pycnodysostosis presenting with seizures and porencephalic cystsQ42113908
Cathepsin D expression in chronic plaque psoriasis: an immunohistochemical study.Q42494725
Bone density, turnover, and estimated strength in postmenopausal women treated with odanacatib: a randomized trialQ42713320
The cathepsin K inhibitor odanacatib suppresses bone resorption in women with breast cancer and established bone metastases: results of a 4-week, double-blind, randomized, controlled trialQ42781348
Papilledema from craniosynostosis in pycnodysostosisQ42822009
A novel missense mutation in cathepsin K (CTSK) gene in a consanguineous Pakistani family with pycnodysostosisQ43122647
The resorptive apparatus of osteoclasts supports lysosomotropism and increases potency of basic versus non-basic inhibitors of cathepsin K.Q43185375
Odanacatib, a cathepsin-K inhibitor for osteoporosis: a two-year study in postmenopausal women with low bone densityQ43252754
Treatment with a potent cathepsin K inhibitor preserves cortical and trabecular bone mass in ovariectomized monkeysQ43274929
Understanding coupling between bone resorption and formation: are reversal cells the missing link?Q43405568
High-resolution peripheral quantitative computed tomography and finite element analysis of bone strength at the distal radius in ovariectomized adult rhesus monkey demonstrate efficacy of odanacatib and differentiation from alendronateQ43444356
Human osteoclast cathepsin K is processed intracellularly prior to attachment and bone resorptionQ43558401
Effects of odanacatib on BMD and safety in the treatment of osteoporosis in postmenopausal women previously treated with alendronate: a randomized placebo-controlled trialQ43733116
A novel mutation (R122Q) in the cathepsin K gene in a Chinese child with PyknodysostosisQ43797875
Familial pycnodysostosis: identification of a novel mutation in the CTSK gene (cathepsin K)Q44018132
Differential effects of androgens and estrogens on bone turnover in normal men.Q44273273
Cathepsin K mRNA and protein expression in prostate cancer progressionQ44303172
Clinical, genetic, and cellular analysis of 49 osteopetrotic patients: implications for diagnosis and treatment.Q36927212
Cysteine cathepsins: cellular roadmap to different functionsQ36934250
Regulation of bone formation by osteoclasts involves Wnt/BMP signaling and the chemokine sphingosine-1-phosphate.Q37015968
Cathepsin K inhibitors: a novel target for osteoporosis therapyQ37029906
Odanacatib in postmenopausal women with low bone mineral density: a review of current clinical evidenceQ37058788
Osteoclast-secreted CTHRC1 in the coupling of bone resorption to formationQ37123948
Drug-induced morphea: report of a case induced by balicatib and review of the literatureQ37138210
TGF-β induces Wnt10b in osteoclasts from female mice to enhance coupling to osteoblastsQ37181921
Ablation of cathepsin k activity in the young mouse causes hypermineralization of long bone and growth platesQ37187086
Relative contributions of testosterone and estrogen in regulating bone resorption and formation in normal elderly menQ37272054
TGF-beta1-induced migration of bone mesenchymal stem cells couples bone resorption with formationQ37307155
Expression of the elastolytic cathepsins S and K in human atheroma and regulation of their production in smooth muscle cellsQ37384330
Molecular mechanisms in coupling of bone formation to resorption.Q37385000
Inhibition of osteoblastic bone formation by nuclear factor-kappaB.Q37401772
Cathepsin K inhibitors increase distal femoral bone mineral density in rapidly growing rabbitsQ37427459
Exome sequencing identifies CTSK mutations in patients originally diagnosed as intermediate osteopetrosis.Q37453562
EphrinB2 regulation by PTH and PTHrP revealed by molecular profiling in differentiating osteoblastsQ34796085
Defective growth hormone secretion in children with pycnodysostosis and improved linear growth after growth hormone treatmentQ34799586
Thyroid functions of mouse cathepsins B, K, and L.Q35019251
Odanacatib for the treatment of postmenopausal osteoporosis: development history and design and participant characteristics of LOFT, the Long-Term Odanacatib Fracture TrialQ35033184
Clinical and animal research findings in pycnodysostosis and gene mutations of cathepsin K from 1996 to 2011Q35040136
ONO-5334, a cathepsin K inhibitor, improves bone strength by preferentially increasing cortical bone mass in ovariectomized ratsQ35062434
Pivotal role of cathepsin K in lung fibrosisQ35098381
Inhibition of cathepsin K increases modeling-based bone formation, and improves cortical dimension and strength in adult ovariectomized monkeysQ35109866
Odanacatib treatment affects trabecular and cortical bone in the femur of postmenopausal women: results of a two-year placebo-controlled trialQ35181789
A small molecule, odanacatib, inhibits inflammation and bone loss caused by endodontic diseaseQ35187625
Increased fracture callus mineralization and strength in cathepsin K knockout miceQ35188085
Cell line IDG-SW3 replicates osteoblast-to-late-osteocyte differentiation in vitro and accelerates bone formation in vivoQ35332147
Odanacatib: a review of its potential in the management of osteoporosis in postmenopausal womenQ35589110
A 2003 update of bone physiology and Wolff's Law for cliniciansQ35706996
Decreased bone turnover and deterioration of bone structure in two cases of pycnodysostosisQ35740740
Silencing of parathyroid hormone (PTH) receptor 1 in T cells blunts the bone anabolic activity of PTHQ35849800
Characterization of circulating osteoblast lineage cells in humansQ35894606
Osteoclast-derived activity in the coupling of bone formation to resorption.Q36032429
Estrogen and the skeletonQ36179747
Matrix IGF-1 maintains bone mass by activation of mTOR in mesenchymal stem cellsQ36223256
Odanacatib, A Cathepsin K-Specific Inhibitor, Inhibits Inflammation and Bone Loss Caused by Periodontal DiseasesQ36289023
Mice, double deficient in lysosomal serine carboxypeptidases Scpep1 and Cathepsin A develop the hyperproliferative vesicular corneal dystrophy and hypertrophic skin thickenings.Q36289890
Decreased c-Src expression enhances osteoblast differentiation and bone formationQ36366926
Building bone to reverse osteoporosis and repair fracturesQ36407024
Intermittent parathyroid hormone administration converts quiescent lining cells to active osteoblastsQ36486277
Cathepsin K knockout mitigates high-fat diet-induced cardiac hypertrophy and contractile dysfunctionQ36560578
Osteoclast-specific cathepsin K deletion stimulates S1P-dependent bone formationQ36580426
Sphingosine 1-phosphate (S1P) receptors 1 and 2 coordinately induce mesenchymal cell migration through S1P activation of complementary kinase pathwaysQ36636026
Tartrate-resistant acid phosphatase 5b (TRACP 5b) as a marker of bone resorption.Q36641421
The molecular understanding of osteoclast differentiationQ36650749
Insights into material and structural basis of bone fragility from diseases associated with fractures: how determinants of the biomechanical properties of bone are compromised by disease.Q36697904
Are nonresorbing osteoclasts sources of bone anabolic activity?Q36709511
Impaired osteoclastic bone resorption leads to osteopetrosis in cathepsin-K-deficient miceQ36791739
Odanacatib, a selective cathepsin K inhibitor to treat osteoporosis: safety, tolerability, pharmacokinetics and pharmacodynamics--results from single oral dose studies in healthy volunteers.Q36792968
Bone resorption and formation on the periosteal envelope of the ilium: a histomorphometric study in healthy womenQ44783413
Osteoclast-derived serum tartrate-resistant acid phosphatase 5b in Albers-Schonberg disease (type II autosomal dominant osteopetrosis).Q44796989
Osteoclast deficiency results in disorganized matrix, reduced mineralization, and abnormal osteoblast behavior in developing boneQ45018962
Increased presence of capillaries next to remodeling sites in adult human cancellous bone.Q45881370
Expression and regulation of cathepsin K in skin fibroblasts.Q45996302
Effect of the cathepsin K inhibitor odanacatib on bone resorption biomarkers in healthy postmenopausal women: two double-blind, randomized, placebo-controlled phase I studies.Q46022677
Molecular analysis of a novel cathepsin K gene mutation in a Chinese child with pycnodysostosisQ46122811
Odanacatib Restores Trabecular Bone of Skeletally Mature Female Rabbits With Osteopenia but Induces Brittleness of Cortical Bone: A Comparative Study of the Investigational Drug With PTH, Estrogen, and AlendronateQ46279925
Odanacatib increases mineralized callus during fracture healing in a rabbit ulnar osteotomy model.Q46280547
Human osteoblasts produce cathepsin K.Q46282719
Reduced osteoblastic population and defective mineralization in osteopetrotic (op/op) miceQ46283054
Effects of Odanacatib on bone mineralization density distribution in thoracic spine and femora of ovariectomized adult rhesus monkeys: a quantitative backscattered electron imaging study.Q46289368
Cathepsins B, K, and L are regulated by a defined collagen type II peptide via activation of classical protein kinase C and p38 MAP kinase in articular chondrocytesQ46908223
Effect of cathepsin k inhibitor basicity on in vivo off-target activitiesQ46947736
Response of biochemical markers of bone turnover to hormone replacement therapy: impact of biological variability.Q47857557
Effect of ONO-5334 on bone mineral density and biochemical markers of bone turnover in postmenopausal osteoporosis: 2-year results from the OCEAN study.Q47966083
Plexin-A1 and its interaction with DAP12 in immune responses and bone homeostasisQ50335578
Increased expression and activation of cathepsin K in human osteoarthritic cartilage and synovial tissuesQ50438836
Loss of osteocyte integrity in association with microdamage and bone remodeling after fatigue in vivo.Q50514494
Sema3A regulates bone-mass accrual through sensory innervations.Q50745844
A novel mutation in two families with pycnodysostosis.Q50978170
Expression of cathepsin K and tartrate-resistant acid phosphatase is not confined to osteoclasts but is a general feature of multinucleated giant cells: systematic analysis.Q50993445
Atypical femur fractures in a patient with pycnodysostosis: a case report.Q51019184
Odanacatib, a selective cathepsin K inhibitor, demonstrates comparable pharmacodynamics and pharmacokinetics in older men and postmenopausal women.Q51182200
Effect of the cathepsin K inhibitor odanacatib administered once weekly on bone mineral density in Japanese patients with osteoporosis--a double-blind, randomized, dose-finding study.Q51239894
Balicatib, a cathepsin K inhibitor, stimulates periosteal bone formation in monkeys.Q51506177
A highly potent inhibitor of cathepsin K (relacatib) reduces biomarkers of bone resorption both in vitro and in an acute model of elevated bone turnover in vivo in monkeys.Q51787069
Mice lacking cathepsin K maintain bone remodeling but develop bone fragility despite high bone mass.Q51801651
Cathepsin K expression in human lung.Q52167712
Regulation of osteoclast differentiation and function by receptor activator of NFkB ligand and osteoprotegerin.Q53959402
Determination of bone markers in pycnodysostosis: effects of cathepsin K deficiency on bone matrix degradation.Q54071347
Ultrastructural investigations of bone resorptive cells in two types of autosomal dominant osteopetrosis.Q54227754
Novel CTSK mutation resulting in an entire exon 2 skipping in a Thai girl with pycnodysostosis.Q54239113
Mechanical loading stimulates bone formation by reactivation of bone lining cells in 13-week-old rats.Q54601079
Circulating osteoblast-lineage cells in humans.Q54664097
Non-resorbing osteoclasts induce migration and osteogenic differentiation of mesenchymal stem cells.Q54706728
Differentiation potential of a mouse bone marrow stromal cell line.Q54722455
Craniosynostosis in pycnodysostosis: broadening the spectrum of the cranial flat bone abnormalitiesQ56331110
Cardiotrophin-1 Is an Osteoclast-Derived Stimulus of Bone Formation Required for Normal Bone RemodelingQ57265515
Cathepsin K Knockout Mice Develop Osteopetrosis Due to a Deficit in Matrix Degradation but Not DemineralizationQ57272396
Bidirectional ephrinB2-EphB4 signaling controls bone homeostasisQ57675131
Bisphosphonate-Associated Osteonecrosis of the Jaw: Report of a Task Force of the American Society for Bone and Mineral ResearchQ58216587
Odanacatib in the treatment of postmenopausal women with low bone mineral density: Three-year continued therapy and resolution of effectQ58970743
Suggested Sequential Mode of Control of Changes in Cell Behaviour in Adult Bone RemodellingQ59076842
Activation of the bone-derived latent TGF beta complex by isolated osteoclastsQ61961261
Upper airway surgery of obstructive sleep apnea in pycnodysostosis: Case report and literature reviewQ62065401
The coupling of bone formation to bone resorption: a critical analysis of the concept and of its relevance to the pathogenesis of osteoporosisQ70459032
Pycnodysostosis: refined linkage and radiation hybrid analyses reduce the critical region to 2 cM at 1q21 and map two candidate genesQ71235368
Evidence that intermittent treatment with parathyroid hormone increases bone formation in adult rats by activation of bone lining cellsQ71940337
P921main subjectlessons learnedQ1673259
osteoporosisQ165328
P577publication date2017-06-23
P1433published inEndocrine ReviewsQ3054007
P1476titleCathepsin K Inhibitors for Osteoporosis: Biology, Potential Clinical Utility, and Lessons Learned

Reverse relations

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