Effects of inflammation on bone: an update.

University of California, Department of Medicine, San Francisco VA Medical Center, San Francisco, CA, USA
Current opinion in rheumatology (Impact Factor: 5.07). 07/2011; 23(4):389-95. DOI: 10.1097/BOR.0b013e3283474dbe
Source: PubMed

ABSTRACT To present an updated summary of the relationship between inflammation and localized and generalized bone loss in the rheumatic diseases.
In addition to the well established role of inflammatory cytokines in promoting enhanced osteoclast function and bone loss, recent work has discovered the cytokine milieu may also inhibit osteoblast function and bone repair. The WNT and bone morphogenetic protein pathways provide molecular links between inflammation and altered bone homeostasis in chronic inflammatory states. These pathways and others have been the targets of emerging therapies for the management of inflammatory bone loss.
Inflammation and bone loss are linked through a number of molecular pathways. Both of these processes need to be addressed when designing an effective treatment strategy for the rheumatic diseases.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Neutrophils and macrophages, as key mediators of inflammation, have defined functionally important roles in mammalian tissue repair. Although recent evidence suggests that similar cells exist in zebrafish and also migrate to sites of injury in larvae, whether these cells are functionally important for wound healing or regeneration in adult zebrafish is unknown. To begin to address these questions, we first tracked neutrophils (lyzC(+), mpo(+)) and macrophages (mpeg1(+)) in adult zebrafish following amputation of the tail fin, and detailed a migratory timecourse that revealed conserved elements of the inflammatory cell response with mammals. Next, we used transgenic zebrafish in which we could selectively ablate macrophages, which allowed us to investigate whether macrophages were required for tail fin regeneration. We identified stage-dependent functional roles of macrophages in mediating fin tissue outgrowth and bony ray patterning, in part through modulating levels of blastema proliferation. Moreover, we also sought to detail molecular regulators of inflammation in adult zebrafish and identified Wnt/β-catenin as a signaling pathway that regulates the injury microenvironment, inflammatory cell migration and macrophage phenotype. These results provide a cellular and molecular link between components of the inflammation response and regeneration in adult zebrafish.
    Development 07/2014; 141(13):2581-91. · 6.27 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Introduction Weight loss reduces co-morbidities of obesity, but decreases bone mass. Purpose Our aims were to 1) determine if adequate dairy intake attenuates weight loss-induced bone loss; 2) evaluate the associations of endocrine, inflammatory and bone markers, anthropometric and other parameters to bone mineral density and content (BMD, BMC) pre- and post-weight loss; 3) model the contribution of these variables to post weight-loss BMD and BMC Methods Overweight/obese women (BMI: 28-37 kg/m2) were enrolled in an energy reduced (-500 kcal/d; -2092 kJ/d) diet with adequate dairy (AD: 3-4 servings/d; n=25, 32.2 + 8.8y) or low dairy (LD: ≤ 1 serving/d; n=26, 31.7 + 8.4 y). BMD, BMC and body composition were measured by DXA. Bone markers (CTX, PYD, BAP, OC), endocrine (PTH, vitamin D, leptin, adiponectin, ghrelin, amylin, insulin, GLP-1, PAI-1, HOMA) and inflammatory markers (CRP, IL1-β, IL-6, IL-8, TNF-α, cortisol) were measured in serum or plasma. PA was assessed by accelerometry. Results Following weight loss, AD intake resulted in significantly greater (p = 0.004) lumbar spine BMD and serum osteocalcin (p=0.004) concentration compared to LD. Pre- and post- body fat were negatively associated with hip and lumbar spine BMC (r = -0.28, p=0.04 to -0.45, p=0.001). Of note were the significant negative associations among bone markers and IL-1β, TNFα and CRP ranging from r = -0.29 (p=0.04) to r = -0.34 (p=0.01); magnitude of associations did not change with weight loss. Adiponectin was negatively related to change in osteocalcin. Factor analysis resulted in 8 pre- and post-weight loss Factors. Pre-weight loss Factors accounted for 13.7% of the total variance in pre-weight loss hip BMD; post-weight loss Factors explained 19.6% of the total variance in post-weight loss hip BMD. None of the Factors contributed to the variance in lumbar spine BMD. Conclusion AD during weight loss resulted in higher lumbar spine BMD and osteocalcin compared to LD. Significant negative associations were observed between bone and inflammatory markers suggesting inflammation suppresses bone metabolism. Using Factor Analysis, 19.6% of total variance in post-weight loss hip BMD could be explained by endocrine, immune, and anthropometric variables, but not lumbar spine BMD.
    Bone 07/2014; · 4.46 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Los agentes biológicos inhibidores del factor de necrosis tumoral alfa (anti-TNF) se constituyen en un avance muy significativo en el tratamiento de los pacientes con espondilitis anquilosante (EA), demostrando una notable mejoría de sus síntomas, de su función y de su calidad de vida. Sumado a esta excelente respuesta clínica, se ha demostrado igualmente mejoría de la inflamación, demostrada mediante pruebas de laboratorio y estudios de resonancia nuclear magnética. A pesar de esta clara evidencia, la conexión entre actividad inflamatoria y progresión estructural no está tan claramente establecida como en artritis reumatoide (AR), y la evidencia de la eficacia de los anti-TNF en la prevención de la progresión del daño radiológico crónico en EA es deficiente. Se revisan las evidencias y las teorías actuales respecto a este crucial tema y se hace mención del importante papel de la proteína DKK-1, inhibidora de la vía Wnt. Esta proteína ha emergido recientemente como un regulador fundamental en la biología ósea y se constituye en una conexión clave entre inflamación, osteoporosis y remodelación articular.
    Revista Colombiana de Reumatología. 01/2012; 19(1):8-17.