Aims. Our aim was to investigate occurrence of senescent cells directly in tendon tissue biopsies from patients with chronic shoulder tendinopathies, and to correlate senescence with Enhancer of zeste 2 (EZH2) expression, the functional subunit of the epigenetic master regulator polycomb repressive complex. Methods. Human proximal long head of biceps tendons from patients with different chronic shoulder pathologies (n = 22), and controls from patients with humerus fracture (n = 6) and pathology (n = 4), were histologically scored for degeneration and analyzed for gene and protein expression of tendon specific factors, senescence markers, and EZH2. Tissues were further exposed to senotherapeutic compounds and the USA Food and Drugs Administration-approved selective EZH2 inhibitor EPZ-6438 and their senescence-associated secretory phenotype (SASP) assessed. Results. Expression of senescence markers (CDKN2A/p16, CDKN2D/p19) and EZH2 was significantly higher in tendinopathies compared to fracture or healthy tissue controls and positively correlated with the degree of tissue degeneration. Immunofluorescent stainings demonstrated colocalization of p16 and p19 with EZH2 in tenocytes. Treatment of tendon biopsies with EPZ-6438 reduced
The ageing population and an increase in both
the incidence and prevalence of cancer pose a healthcare challenge, some
of which is borne by the orthopaedic community in the form of osteoporotic
fractures and metastatic bone disease. In recent years there has
been an increasing understanding of the pathways involved in bone
metabolism relevant to osteoporosis and metastases in bone. Newer
therapies may aid the management of these problems. One group of
drugs, the antibody mediated anti-resorptive therapies (AMARTs)
use antibodies to block bone resorption pathways. This review seeks
to present a synopsis of the guidelines, pharmacology and potential pathophysiology
of AMARTs and other new anti-resorptive drugs. We evaluate the literature relating to AMARTs and new anti-resorptives
with special attention on those approved for use in clinical practice. Denosumab, a monoclonal antibody against Receptor Activator for
Nuclear Factor Kappa-B Ligand. It is the first AMART approved by
the National Institute for Health and Clinical Excellence and the
US Food and Drug Administration. Other novel anti-resorptives awaiting
approval for clinical use include Odanacatib. Denosumab is indicated for the treatment of osteoporosis and
prevention of the complications of bone metastases. Recent evidence
suggests, however, that denosumab may have an adverse event profile
similar to bisphosphonates, including atypical femoral fractures.
It is, therefore, essential that orthopaedic surgeons are conversant
with these medications and their safe usage. Take home message: Denosumab has important orthopaedic indications
and has been shown to significantly reduce patient morbidity in
osteoporosis and metastatic bone disease. Cite this article:
