Small interfering RNAs in the management of human osteoporosis.

BACKGROUND: Osteoporosis results in reduced bone mass and consequent bone fragility. Small interfering RNAs (siRNAs) can be used for therapeutic purposes, as molecular targets or as useful markers to test new therapies. SOURCES OF DATA: A systematic search of different databases to May 2023 was performed to define the role of siRNAs in osteoporosis therapy. Fourteen suitable studies were identified. AREAS OF AGREEMENT: SiRNAs may be useful in studying metabolic processes in osteoporosis and identify possible therapeutic targets for novel drug therapies. AREAS OF CONTROVERSY: The metabolic processes of osteoporosis are regulated by many genes and cytokines that can be targeted by siRNAs. However, it is not easy to predict whether the in vitro responses of the studied siRNAs and drugs are applicable in vivo. GROWING POINTS: Metabolic processes can be affected by the effect of gene dysregulation mediated by siRNAs on various growth factors. AREAS TIMELY FOR DEVELOPING RESEARCH: Despite the predictability of pharmacological response of siRNA in vitro, similar responses cannot be expected in vivo.

Small interfering RNAs in the management of human rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) has unclear pathogenesis, but the molecules that feed its inflammatory state are known. Small interfering RNAs (siRNAs) are useful to identify molecular targets and evaluate the efficacy of specific drugs, and can themselves be used for therapeutic purposes. SOURCES OF DATA: A systematic search of different databases to March 2022 was performed to define the role of siRNAs in RA therapy. Twenty suitable studies were identified. AREAS OF AGREEMENT: Small interfering RNAs can be useful in the study of inflammatory processes in RA, and identify possible therapeutic targets and drug therapies. AREAS OF CONTROVERSY: Many genes and cytokines participate in the inflammatory process of RA and can be regulated with siRNA. However, it is difficult to determine whether the responses to siRNAs and other drugs studied in human cells in vitro are similar to the responses in vivo. GROWING POINTS: Inflammatory processes can be affected by the gene dysregulation of siRNAs on inflammatory cytokines. AREAS TIMELY FOR DEVELOPING RESEARCH: To date, it is not possible to determine whether the pharmacological response of siRNAs on cells in vitro would be similar to what takes place in vivo for the diseases studied so far.

Melatonin and adolescent idiopathic scoliosis: The present evidence.

INTRODUCTION: Adolescent idiopathic scoliosis (AIS) is a multifactorial condition with genetic predisposing factors, and several causes have been put forward for its aetiopathogenesis, including possible hormonal dysfunction. Melatonin seems to play significant role in AIS. METHODS: A systematic search in different database, to July 2021, was performed to define the role of melatonin in the pathophysiology of adolescent idiopathic scoliosis. Eight suitable studies were identified. RESULTS: The concentration and rhythm of melatonin secretion can play an important role by influencing the pathogenesis of adolescent idiopathic scoliosis. CONCLUSIONS: Although there are many alterations of melatonin in subjects with adolescent idiopathic scoliosis, the many variables present do not allow to establish a direct cause-effect relationship. LEVEL OF EVIDENCE: Level IV.

Small interfering RNAs in tendon homeostasis.

BACKGROUND: Tenogenesis and tendon homeostasis are guided by genes encoding for the structural molecules of tendon fibres. Small interfering RNAs (siRNAs), acting on gene regulation, can therefore participate in the process of tendon healing. SOURCES OF DATA: A systematic search of different databases to October 2020 identified 17 suitable studies. AREAS OF AGREEMENT: SiRNAs can be useful to study reparative processes of tendons and identify possible therapeutic targets in tendon healing. AREAS OF CONTROVERSY: Many genes and growth factors involved in the processes of tendinopathy and tendon healing can be regulated by siRNAs. It is however unclear which gene silencing determines the expected effect. GROWING POINTS: Gene dysregulation of growth factors and tendon structural proteins can be influenced by siRNA. AREAS TIMELY FOR DEVELOPING RESEARCH: It is not clear whether there is a direct action of the siRNAs that can be used to facilitate the repair processes of tendons.

Augmentation or reconstruction of PCL? A quantitative review.

PURPOSE: The purpose of this quantitative review is to document effectiveness and complications of posterior cruciate ligament (PCL) surgery and compare outcomes, advantages and disadvantages of reconstructive and augmentation procedures. METHODS: A systematic literature search was performed in PubMed, Medline, Ovid, Google Scholar and Embase databases using the combined keywords "PCL reconstruction," "PCL augmentation," "clinical outcomes" and "functional outcomes" with no limit for year of publication. Articles were included if they reported data on clinical, functional and imaging outcomes who had undergone reconstruction or augmentation of the PCL for management of PCL injuries. Two authors screened the selected articles for title, abstract and full text in accordance with predefined inclusion and exclusion criteria. The methodological quality of all articles was assessed by two authors according to the Coleman methodology score. The critical appraisal was made using the Physiotherapy Evidence Database (PEDro) scale. RESULTS: A total of 34 studies, 22 retrospective, 9 prospective and 5 were randomized control trials were included by full text. The modified Coleman methodology score averaged 70.8 (SD 6.5), median 73 (range from 60 to 82). At IKDC assessment, the average rate of normal (A) and nearly normal (B) outcomes was 89.8% (SD 4.2) (from 85 to 93%; median 91.4) after PCL augmentation and 80.1% (SD 12.4) after PCL reconstruction (from 57.2 to 100%; median 81.8 %) were rated as normal (A) and nearly normal (B). The average Lysholm Knee Scores after PCL augmentation were 93.1 points (SD 1.9) and ranged from 82.1 to 94.2 (median 90.5) after PCL reconstruction. The KT 1000 difference improved from an average preoperative difference of 8.8 mm (SD 0.9) to an average postoperative of 2.1 mm (SD 0.6) after PCL augmentation (average improvement of 6.7 mm (SD 4.7)) and from 8.2 (SD 3.6) to 2.3 mm (SD 2.0) (average improvement of 5.9 mm SD 4.2) after PCL reconstruction. Postoperatively, the Telos stress radiographic side to side difference averagely improved by 8.6 mm (SD 6.1) after PCL augmentation, from 11.1 mm (SD 1.4) to 2.5 mm (SD 0.4), and by 8.0 mm (SD 5.7) after PCL reconstruction, from 11.5 mm (SD 2.2) to 3.5 mm (SD 1.3). CONCLUSIONS: Augmentation and reconstruction procedures are grossly equivalent, but more data examining the long-term functional status, recovery to preinjury daily and sport activities and occurrence of degenerative changes are needed. LEVEL OF EVIDENCE: IV.

Zimmer Natural Nail and ELOS nails in pertrochanteric fractures.

BACKGROUND: Pertrochanteric fractures of the femur in the elderly are very common. As the average age of the population increases, the incidence of such fractures also raises, resulting in high healthcare costs. The type of surgical devices employed for their surgical management influences these costs. METHODS: A comparative clinical study was conducted on patients operated by one single surgeon between December 2018 and November 2020 in a high-volume regional referral centre. All patients who received a Zimmer Natural Nail (ZNN) or ELOS devices were included. RESULTS: In 119 (66.48%) of the 179 fractures, a ZNN nail was used. Post-operatively, the TAD (tip-to-apex distance) was measured at an average value of 17.05 (4.42-41.85) mm and the CalTAD (calcar-referenced TAD) at an average of 20.76 (10.82-43.63) mm. The mean hospitalization time was 10.19 (4-22) days. In the other 60 trochanteric fractures, an ELOS nail was used. Post-operative imaging indicated a TAD of 19.65 (5.08-31.4) mm and a CalTAD of 22.86 mm (12.66-33.77). The average time of the operation was 45.82 (20-110) min. The average period of hospitalization was 10.45 (5-24) days. CONCLUSION: Both devices give similar results in terms of short-term post-operative outcome and hospitalization. The price difference between the devices does not translate in different short-term results on the operated patients.