Mendelian randomization (MR) is considered to overcome the bias of observational studies, but there is no current meta-analysis of MR studies on rheumatoid arthritis (RA). The purpose of this study was to summarize the relationship between potential pathogenic factors and RA risk based on existing MR studies. PubMed, Web of Science, and Embase were searched for MR studies on influencing factors in relation to RA up to October 2022. Meta-analyses of MR studies assessing correlations between various potential pathogenic factors and RA were conducted. Random-effect and fixed-effect models were used to synthesize the odds ratios of various pathogenic factors and RA. The quality of the study was assessed using the Strengthening the Reporting of Observational Studies in Epidemiology using Mendelian Randomization (STROBE-MR) guidelines.Aims
Methods
Degenerative disc disease (DDD) and osteoarthritis (OA) are relatively frequent causes of disability amongst the elderly; they constitute serious socioeconomic costs and significantly impair quality of life. Previous studies to date have found that aggrecan variable number of tandem repeats (VNTR) contributes both to DDD and OA. However, current data are not consistent across studies. The purpose of this study was to evaluate systematically the relationship between aggrecan VNTR, and DDD and/or OA. This study used a highly sensitive search strategy to identify all published studies related to the relationship between aggrecan VNTR and both DDD and OA in multiple databases from January 1996 to December 2016. All identified studies were systematically evaluated using specific inclusion and exclusion criteria. Cochrane methodology was also applied to the results of this study.Objectives
Methods
Objectives. Bisphosphonates are widely used as first-line treatment for primary and secondary prevention of fragility fractures. Whilst they have proved effective in this role, there is growing concern over their long-term use, with much evidence linking bisphosphonate-related suppression of bone remodelling to an increased risk of atypical subtrochanteric fractures of the femur (AFFs). The objective of this article is to review this evidence, while presenting the current available strategies for the management of AFFs. Methods. We present an evaluation of current literature relating to the pathogenesis and treatment of AFFs in the context of bisphosphonate use. Results. Six broad themes relating to the pathogenesis and management of bisphosphonate-related AFFs are presented. The key themes in fracture pathogenesis are: bone microdamage accumulation; altered bone mineralisation and altered collagen formation. The key themes in fracture management are: medical therapy and surgical therapy. In addition,
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:
Neurogenic heterotopic ossification (NHO) is
a disorder of aberrant bone formation affecting one in five patients sustaining
a spinal cord injury or traumatic brain injury. Ectopic bone forms
around joints in characteristic patterns, causing pain and limiting
movement especially around the hip and elbow. Clinical sequelae
of neurogenic heterotopic ossification include urinary tract infection,
pressure injuries, pneumonia and poor hygiene, making early diagnosis
and treatment clinically compelling. However, diagnosis remains
difficult with more investigation needed. Our pathophysiological
understanding stems from mechanisms of basic bone formation enhanced
by evidence of systemic influences from circulating humor factors
and perhaps neurological ones. This increasing understanding guides
our implementation of current prophylaxis and treatment including
the use of non-steroidal anti-inflammatory drugs, bisphosphonates,
radiation therapy and surgery and, importantly, should direct future, more
effective ones.
Osteoporosis is common and the health and financial
cost of fragility fractures is considerable. The burden of cardiovascular
disease has been reduced dramatically by identifying and targeting
those most at risk. A similar approach is potentially possible in
the context of fragility fractures. The World Health Organization
created and endorsed the use of FRAX, a fracture risk assessment
tool, which uses selected risk factors to calculate a quantitative,
patient-specific, ten-year risk of sustaining a fragility fracture.
Treatment can thus be based on this as well as on measured bone
mineral density. It may also be used to determine at-risk individuals,
who should undergo bone densitometry. FRAX has been incorporated
into the national osteoporosis guidelines of countries in the Americas,
Europe, the Far East and Australasia. The United Kingdom National
Institute for Health and Clinical Excellence also advocates its
use in their guidance on the assessment of the risk of fragility
fracture, and it may become an important tool to combat the health
challenges posed by fragility fractures.
Antiplatelet agents are widely prescribed for the primary and secondary prevention of cardiovascular events. A common clinical problem facing orthopaedic and trauma surgeons is how to manage patients receiving these agents who require surgery, either electively or following trauma. The dilemma is to balance the risk of increased blood loss if the antiplatelet agents are continued peri-operatively against the risk of coronary artery/stent thrombosis and/or other vascular event if the drugs are stopped. The traditional approach of stopping these medications up to two weeks before surgery appears to pose significant danger to patients and may require review. This paper covers the important aspects regarding the two most commonly prescribed antiplatelet agents, aspirin and clopidogrel.
Heterotopic ossification following joint replacement in the lower limb occurs in 3% to 90% of cases. Higher grades of heterotopic ossification can result in significant limitation of function and can negate the benefits of joint replacement. The understanding of the pathophysiology of this condition has improved in recent years. It would appear to be related to a combination of systemic and local factors, including over-expression of bone morphogenetic protein-4. There is currently little evidence to support the routine use of prophylaxis for heterotopic ossification in arthroplasty patients, but prophylaxis is recommended by some for high-risk patients. Radiotherapy given as one dose of 7 Gy to 8 Gy, either pre-operatively (<
four hours before) or post-operatively (within 72 hours of surgery), appears to be more effective than indometacin therapy (75 mg daily for six weeks). In cases of prophylaxis against recurrent heterotopic ossification following excision, recent work has suggested that a combination of radiotherapy and indometacin is effective. Advances in our understanding of this condition may permit the development of newer, safer treatment modalities.