Background: Microfracture is a frequently used technique for the repair of articular cartilage lesions of the knee. Despite the popularity of the technique, prospective information about the clinical results after microfracture is still limited. The purpose of our study was to identify the factors that affect the clinical outcome from this cartilage repair technique.

Methods: Forty-eight symptomatic patients with isolated full-thickness articular cartilage defects of the femur in a stable knee were treated with the microfracture technique. Prospective evaluation of patient outcome was performed for a minimum follow-up of twenty-four months with a combination of validated outcome scores, subjective clinical rating, and cartilage-sensitive magnetic resonance imaging.

Results: At the time of the latest follow-up, knee function was rated good to excellent for thirty-two patients (67%), fair for twelve patients (25%), and poor for four (8%). Significant increases in the activities of daily living scores, International Knee Documentation Committee scores, and the physical component score of the Short Form-36 were demonstrated after microfracture (p 30 kg/m2. Significant improvement in the activities of daily living score was more frequent with a preoperative duration of symptoms of less than twelve months (p < 0.05). Magnetic resonance imaging in twenty-four knees demonstrated good repair-tissue fill in the defect in thirteen patients (54%), moderate fill in seven (29%), and poor fill in four patients (17%). The fill grade correlated with the knee function scores. All knees with good fill demonstrated improved knee function, whereas poor fill grade was associated with limited improvement and decreasing functional scores after twenty-four months.

Conclusions: Microfracture repair of articular cartilage lesions in the knee results in significant functional improvement at a minimum follow-up of two years. The best short-term results are observed with good fill grade, low body-mass index, and a short duration of preoperative symptoms. A high body-mass index adversely affects short-term outcome, and a poor fill grade is associated with limited short-term durability.

Level of Evidence: Therapeutic Level IV. See Instructions to Authors for a complete description of levels of evidence.

The microfracture technique for the treatment of articular cartilage lesions in the knee : A prospective cohort study

https://nutricaoclinicaeesteticabh.files.wordpress.com/2011/11/aging-osteoar-senes.pdf

Aging and osteoarthritis: the role of chondrocyte senescence and aging changes in the cartilage matrix

Objective
It has been suggested that subchondral bone remodeling plays a role in the progression of osteoarthritis (OA). To test this hypothesis, we characterized the changes in the rat anterior cruciate ligament transection (ACLT) model of OA and evaluated the effects of alendronate (ALN), a potent inhibitor of bone resorption, on cartilage degradation and on osteophyte formation.

Methods
Male Sprague-Dawley rats underwent ACLT or sham operation of the right knee. Animals were then treated with ALN (0.03 and 0.24 μg/kg/week subcutaneously) and necropsied at 2 or 10 weeks postsurgery. OA changes were evaluated. Subchondral bone volume and osteophyte area were measured by histomorphometric analysis. Coimmunostaining for transforming growth factor β (TGFβ), matrix metalloproteinase 9 (MMP-9), and MMP-13 was performed to investigate the effect of ALN on local activation of TGFβ.

Results
ALN was chondroprotective at both dosages, as determined by histologic criteria and collagen degradation markers. ALN suppressed subchondral bone resorption, which was markedly increased 2 weeks postsurgery, and prevented the subsequent increase in bone formation 10 weeks postsurgery, in the untreated tibial plateau of ACLT joints. Furthermore, ALN reduced the incidence and area of osteophytes in a dose-dependent manner. ALN also inhibited vascular invasion into the calcified cartilage in rats with OA and blocked osteoclast recruitment to subchondral bone and osteophytes. ALN treatment reduced the local release of active TGFβ, possibly via inhibition of MMP-13 expression in articular cartilage and MMP-9 expression in subchondral bone.

Conclusion
Subchondral bone remodeling plays an important role in the pathogenesis of OA. ALN or other inhibitors of bone resorption could potentially be used as disease-modifying agents in the treatment of OA.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/art.20124

The role of subchondral bone remodeling in osteoarthritis: reduction of cartilage degeneration and prevention of osteophyte formation by alendronate in the rat anterior cruciate ligament transection model.

Obesity is associated with a range of disabling musculoskeletal conditions in adults. As the prevalence of obesity increases, the societal burden of these chronic musculosketelal conditions, in terms of disability, health-related quality of life, and health-care costs, also increases. Research exploring the nature and strength of the associations between obesity and musculoskeletal conditions is accumulating, providing a better understanding of underlying mechanisms. Weight reduction is important in ameliorating some of the manifestations of musculoskeletal disease and improving function.

The impact of obesity on the musculoskeletal system

We have compiled from literature and other sources a list of 1261 proteins believed to be differentially expressed in human cancer. These proteins, only some of which have been detected in plasma to date, represent a population of candidate plasma biomarkers that could be useful in early cancer detection and monitoring given sufficiently sensitive specific assays. We have begun to prioritize these markers for future validation by frequency of literature citations, both total and as a function of time. The candidates include proteins involved in oncogenesis, angiogenesis, development, differentiation, proliferation, apoptosis, hematopoiesis, immune and hormonal responses, cell signaling, nucleotide function, hydrolysis, cellular homing, cell cycle and structure, the acute phase response and hormonal control. Many have been detected in studies of tissue or nuclear components; nevertheless we hypothesize that most if not all should be present in plasma at some level. Of the 1261 candidates only 9 have been approved as "tumor associated antigens" by the FDA. We propose that systematic collection and large-scale validation of candidate biomarkers would fill the gap currently existing between basic research and clinical use of advanced diagnostics.

/pdf/a-list-of-candidate-cancer-biomarkers-for-targeted-lu8garq70x.pdf

A list of candidate cancer biomarkers for targeted proteomics.

Background: Cartilage normally has a slow turnover but in arthritis increased metabolism results in degradation of the tissue. 

Objective: To assess cartilage turnover in a sample of the general population by an assay measuring cartilage derived urinary collagen type II (CTX-II) C-telopeptide degradation products. 

Methods: CTX-II concentrations were measured in urine samples from 615 healthy men and women aged 20–87 years, and the influence of age, sex, menopause, hormone replacement therapy (HRT), and body mass index (BMI) was assessed. 

Results: CTX-II concentrations showed age dependent variations, with notable differences between men and women. Mean (SD) CTX-II concentration in postmenopausal women (220 (118) ng/mmol, n=25) was significantly higher than in an age matched group of premenopausal women (112 (79) ng/mmol, n=26, p<0.001). CTX-II concentration in women using HRT (118 (57) ng/mmol, n=50) was significantly lower than in an age and BMI matched group of women not receiving HRT (215 (99) ng/mmol, n=50, p<0.001). In subjects with a BMI ≥25 kg/m2, CTX-II concentrations were significantly higher than in those with a BMI <25 kg/m2 (185 (114) v 148 (91) ng/mmol, p<0.001). 

Conclusions: Cartilage turnover, as assessed by measuring urinary degradation products of CTX-II varies considerably with age, and significant differences between CTX-II levels in men and women as well as in pre- and postmenopausal women are found. Further studies are required to validate the marker for assessing cartilage degradation in arthritis.

https://ard.bmj.com/content/annrheumdis/62/4/332.full.pdf

Cartilage turnover assessed with a newly developed assay measuring collagen type II degradation products: influence of age, sex, menopause, hormone replacement therapy, and body mass index

Background: Animal studies of arthritis have suggested that bisphosphonates may have chondroprotective abilities. 

Objective: To evaluate the effect of bisphosphonate treatment on cartilage degradation. 

Methods: Type II collagen is almost exclusively localised in cartilage, where it is the major structural component of the tissue. Hence fragments derived from this protein should represent a specific index for cartilage degradation. The urinary concentration of collagen type II C-telopeptide degradation products (CTX-II) was measured by a new immunoassay (enzyme linked immunosorbent assay (ELISA)). The serum concentration of collagen type I C-telopeptide degradation products (CTX-I), a marker of bone degradation, was also measured by ELISA. 

Participants: Two groups were studied. The alendronate group included 63 healthy postmenopausal women aged 45–54 randomly allocated to receive three years' treatment with 1 mg, 5 mg, 10 mg, or 20 mg alendronate daily or placebo. In the third year the women receiving 20 mg were switched to placebo. The ibandronate group included 119 women at least 10 years after the menopause aged <75 randomly allocated to receive 12 months' treatment with 0.25 mg, 0.5 mg, 1.0 mg, 2.5 mg, or 5 mg ibandronate daily or placebo followed by 12 months without treatment. 

Results: 20 mg of alendronate and 2.5 and 5 mg of ibandronate treatment produced significant decreases in urinary CTX-II to about 50% of baseline. The level reached after three months of treatment remained practically constant during the following 12–36 treatment months. When treatment was withdrawn CTX-II values returned towards baseline. Serum CTX-I also decreased rapidly within three months, but to a level of about 30% of baseline. 

Conclusions: The urinary excretion of CTX-II, a new marker of cartilage degradation, decreases significantly in response to bisphosphonate. This suggests that bisphosphonates may have chondroprotective effects in humans. By measurement of CTX-II it should be possible to monitor the effects of drugs that potentially inhibit cartilage destruction.

https://ard.bmj.com/content/annrheumdis/61/6/530.full.pdf

Effect of bisphosphonates on cartilage turnover assessed with a newly developed assay for collagen type II degradation products

Oral ibandronate: changes in markers of bone turnover during adequately dosed continuous and weekly therapy and during different suboptimally dosed treatment regimens.

Of increasing prevalence, diabetes is characterised by elevated blood glucose and chronic inflammation that precedes the onset of multiple secondary complications, including those of the kidney and the eye. As the leading cause of end stage renal disease and blindness in the working population, more than ever is there a demand to develop clinical interventions which can both delay and prevent disease progression. Connexins are membrane bound proteins that can form pores (hemichannels) in the cell membrane. Gated by cellular stress and injury, they open under pathophysiological conditions and in doing so release ‘danger signals’ including adenosine triphosphate into the extracellular environment. Linked to sterile inflammation via activation of the nod-like receptor protein 3 inflammasome, targeting aberrant hemichannel activity and the release of these danger signals has met with favourable outcomes in multiple models of disease, including secondary complications of diabetes. In this review, we provide a comprehensive update on those studies which document a role for aberrant connexin hemichannel activity in the pathogenesis of both diabetic eye and kidney disease, ahead of evaluating the efficacy of blocking connexin-43 specific hemichannels in these target tissues on tissue health and function.

/pdf/connexin-43-a-target-for-the-treatment-of-inflammation-in-3g8gqajn.pdf

Connexin 43: A Target for the Treatment of Inflammation in Secondary Complications of the Kidney and Eye in Diabetes

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Papers

Cartilage turnover assessed with a newly developed assay measuring collagen type II degradation products: influence of age, sex, menopause, hormone replacement therapy, and body mass index

Effect of bisphosphonates on cartilage turnover assessed with a newly developed assay for collagen type II degradation products

Oral ibandronate: changes in markers of bone turnover during adequately dosed continuous and weekly therapy and during different suboptimally dosed treatment regimens.

Connexin 43: A Target for the Treatment of Inflammation in Secondary Complications of the Kidney and Eye in Diabetes