Glenoid exposure is the name of the game in total shoulder arthroplasty. I can honestly say that it took me more than 5 years but less than 10 to feel confident exposing any glenoid, regardless of the degree of bone deformity and the severity of soft-tissue contracture. This lecture represents the synthesis of my experience exposing some of the most difficult glenoids. The basic principles are performing extensive soft-tissue release, minimizing the anteroposterior dimension of the humerus by osteophyte excision, making an accurate humeral neck cut, having a plethora of glenoid retractors, and knowing where to place them. The ten tips, in reverse order of importance are: 10.) Tilt the table away from operative side—this helps face the surface of the glenoid, especially in cases of posterior wear, toward the surgeon. 9.) Have multiple glenoid retractors—these include a large Darrach, a reverse double-pronged Bankart, one or two blunt Homans, small and large Fukudas. 8.) Remove all humeral osteophytes before attempting to retract the humerus posteriorly to expose the glenoid—this helps to decrease the overall anteroposterior dimension of the humerus and allows for maximum posterior displacement of the humerus. 7.) Make an accurate humeral neck cut—even 5mm of extra humeral bone will make glenoid exposure difficult. 6.) Optimal humeral position—it has been taught that abduction, external rotation, and extension is the optimal position. It may vary with each case. Therefore, experiment with humeral rotation to find the position that allows maximum visualization. This is often the position that makes the cut surface of the humerus parallel to the surface of the glenoid. 5.) Optimal retractor placement—my typical retractor placement is a Fukuda on the posterior lip of the glenoid, a reverse double-pronged Bankart on the anterior neck of the scapula, and a blunt Homan posterosuperiorly. Occasionally, a second blunt Homan anteroinferiorly is helpful, particularly in muscular males with a large pectoralis major. 4.) Laminar spreader for lateral humeral displacement—this can be helpful for posterior capsulorrhaphy or for posterior glenoid bone grafting. 3.) Maximal humeral capsular release—the release of the anterior capsule from the humerus must go well past the 6 o'clock position and up the posterior surface of the humerus. This aides in humeral exposure but also allows for more posterior displacement of the humerus during glenoid exposure. 2.) Anteroinferior capsular release or excision—extensive anteroinferior release or excision (my preference), allows for maximal posterior humeral displacement and also restores external rotation. 1.) Posterior or posteroinferior capsular release—release of the posteroinferior corner of the capsule from the glenoid results in a noticeable increase in posterior humeral retractability. In cases without substantial posterior subluxation, extensive release of the entire posterior capsule is performed.
Neurovascular injury during shoulder arthroplasty is uncommon and has been reported to occur in 1–4% of cases. The incidence of nerve abnormalities during intraoperative nerve monitoring during shoulder arthroplasty is substantially higher. However, the rate of false positives with nerve monitoring is high and the clinical significance of these intraoperative findings is unknown. Therefore, the clinical utility of intraoperative nerve monitoring is unproven. Regardless, experience with intraoperative nerve monitoring has allowed us to identify the times during the procedure when measurable nerve dysfunction is most common. Moreover, experience as well as familiarity with reported patient and anatomic risk factors may help reduce the incidence of neurovascular injury. Five rules that will likely help to reduce intraoperative nerve injuries include recognition of reported patient risk factors, knowledge of relevant anatomy and normal anatomic variations, intraoperative identification and protection of at-risk neurovascular structures, limitation of overall operative time and the amount of time with the arm in at-risk positions, and minimization of retraction force. It is likely not possible to completely avoid neurovascular injuries during TSA. However, by following these five rules, the risk of neurovascular injury can be minimised.
Clinical nerve injury has been reported in 0.6–4.8% of shoulder arthroplasties. Classical teaching is that 70–85% of injuries recover. Despite recovery of motor function, overall shoulder function may be negatively affected and residual pain is common. Complex regional pain syndromes may develop and become permanent. Consequently, methods to limit nerve injury have been investigated. In the early 2000's I became concerned about the incidence of nerve injuries in my arthroplasty practice. I became intrigued with the idea of peripheral nerve monitoring as a method to alert the surgeon intra-operatively about impending nerve insults so that evasive measures could be taken to prevent any clinically significant nerve injuries. The results of our first 30 consecutive patients were published in JSES in 2007. Seventeen patients (56.7%) had 30 episodes of nerve dysfunction (i.e. nerve alerts) during surgery. Twenty-three of thirty alerts (76.7%) returned to normal after repositioning the arm to a neutral position. Post-operative EMG was positive in 4 of 7 (57.1%) patients who did not have a return to normal motor latency intra-operatively and in 1 of 10 (10%) patients whose intra-operative nerve function did return to normal. None had clinical nerve injuries. This early experience indicated that nerve injury was potentially more common than previously thought but intra-operative nerve monitoring seemed to have a relatively high false positive rate. Our group subsequently studied 440 shoulder arthroplasty cases. The protocol used to identify a nerve alert was made more restrictive than the first study as an attempt to decrease the false positive rate. In this larger group, nerve alerts occurred in 185 cases (42.0%), and 37 (8.4%) cases did not have signals return to above the alert threshold at closure. There were no permanent post-operative nerve injuries and 5 transient nerve injuries (1.1%). Cases in which MEP amplitudes remained below alert threshold were significantly more likely to have a post-operative nerve injury (p = 0.03). There were no false negatives, (i.e. a post-operative nerve injury occurred while MEPs were normal at closure), making sensitivity 100%. There were 32 false positives, leading to a specificity of 92.6%, a positive predictive value (PPV) of 13.5%, a negative predictive value (NPV) of 100%, and an accuracy (ACC) of 92.3%. In my opinion, the high false positive rate and the low PPV make the technique difficult to justify for routine clinical use.
Glenoid exposure is the name of the game in total shoulder arthroplasty. I can honestly say that it took me more than 5 years but less than 10 to feel confident exposing any glenoid, regardless of the degree of bone deformity and the severity of soft-tissue contracture. This lecture represents the synthesis of my experience exposing some of the most difficult glenoids. The basic principles are performing extensive soft-tissue release, minimizing the anteroposterior dimension of the humerus by osteophyte excision, making an accurate humeral neck cut, having a plethora of glenoid retractors, and knowing where to place them. The ten tips, in reverse order of importance are: 10.) Tilt the table away from operative side—this helps face the surface of the glenoid, especially in cases of posterior wear, toward the surgeon. 9.) Have multiple glenoid retractors—these include a large Darrach, a reverse double-pronged Bankart, one or two blunt Homans, small and large Fukudas. 8.) Remove all humeral osteophytes before attempting to retract the humerus posteriorly to expose the glenoid—this helps to decrease the overall anteroposterior dimension of the humerus and allows for maximum posterior displacement of the humerus. 7.) Make an accurate humeral neck cut—even 5mm of extra humeral bone will make glenoid exposure difficult. 6.) Optimal humeral position—it has been taught that abduction, external rotation, and extension is the optimal position. It may vary with each case. Therefore, experiment with humeral rotation to find the position that allows maximum visualization. This is often the position that makes the cut surface of the humerus parallel to the surface of the glenoid. 5.) Optimal retractor placement—my typical retractor placement is a Fukuda on the posterior lip of the glenoid, a reverse double-pronged Bankart on the anterior neck of the scapula, and a blunt Homan posterosuperiorly. Occasionally, a second blunt Homan anteroinferiorly is helpful, particularly in muscular males with a large pectoralis major. 4.) Laminar spreader for lateral humeral displacement—this can be helpful for posterior capsulorrhaphy or for posterior glenoid bone grafting. 3.) Maximal humeral capsular release—the release of the anterior capsule from the humerus must go well past the 6 o'clock position and up the posterior surface of the humerus. This aides in humeral exposure but also allows for more posterior displacement of the humerus during glenoid exposure. 2.) Anteroinferior capsular release or excision—extensive anteroinferior release or excision (my preference), allows for maximal posterior humeral displacement and also restores external rotation. 1.) Posterior or posteroinferior capsular release—release of the posteroinferior corner of the capsule from the glenoid results in a noticeable increase in posterior humeral retractability. In cases without substantial posterior subluxation, extensive release of the entire posterior capsule is performed. Following these steps will help the surgeon to gain adequate glenoid exposure, even in the most difficult cases.
Periprosthetic joint infection (PPJI) following shoulder arthroplasty is uncommon, with an overall rate of 0.98%. However, the rates following revision arthroplasty and reverse arthroplasty are much higher. Given the rapid increase in the prevalence of shoulder arthroplasty and the increasing revision burden, the cost of PPJI to society will likely increase substantially. The most common organisms found in PPJI following shoulder arthroplasty are Staphylococcus aureus, coagulase-negative Staphylococcus, and Propionibacterium acnes (P. acnes). P. acnes is especially common in males. Traditional testing for PPJI includes aspiration, white blood cell count (WBC), erythrocyte sedimentation rate (ESR), and c-reactive protein (CRP). Aspiration often yields a dry tap and when fluid is obtained for culture, a positive result is helpful but a negative result does not rule out PPJI. Although WBC, ESR, and CRP are often positive with PPJI in the lower extremity, they are most often negative in shoulder PPJI. Although bone scans and WBC labeled scans are used, they are expensive and have low sensitivity and specificity. New testing and techniques have been reported in an attempt to improve sensitivity and specificity for PPJI. These techniques can be divided into tests on serum, synovial fluid, and tissue. Serum Interleukin-6 (IL-6) is highly specific (94%) for shoulder PPJI but has low sensitivity (14%). Synovial fluid can be tested for leukocyte esterase using a simple and cheap technique. In lower extremity PPJI it has shown to be helpful. It is not as helpful in shoulder PPJI with 30% sensitivity and 67% specificity. Alpha defensin has been reported to be more sensitive (63%) and as specific (95%) as traditional techniques but still lacks predictive value. Testing for specific cytokines (IL-2, IL-6, TNF- α) within synovial fluid is not widely used as yet but has shown promise with 80% sensitivity and 90% specificity. Obtaining tissue for culture and other testing is probably the most reliable way of confirming PPJI for the shoulder. Frozen sections taken at the time of revision can be helpful but is very pathologist dependent and institution specific. With a dedicated musculoskeletal pathologist, the finding of 10 or more WBCs per high powered field has been reported to be 72% sensitive and 100% specific for P. acnes and 63% sensitive and 100% specific for other organisms. Cultures from arthroscopic tissue biopsy have also been found to have high sensitivity (100%) and specificity (100%). Genetic testing of tissue biopsy specimens (PCR/NGS) has recently been reported and shows great promise. The significance of positive cultures and other tests, especially for P. acnes is unclear. There is a high rate of positive intra-operative cultures in primary cases of shoulder arthroplasty. In addition, intra-operative cultures taken at the time of revision, even in cases in which infection is not suspected, are frequently positive for P. acnes with weak correlation with rates of post-operative clinical infection. In conclusion, shoulder PPJI is a difficult problem to deal with. The definition of shoulder PPJI is currently unclear and further study is needed. There is no ideal test to confirm it. A reasonable approach is to aspirate for culture, and perform serum tests for WBC, ESR, and C-reactive protein. If any of these is positive in the setting of a painful arthroplasty, PPJI should be assumed until proven otherwise. Operative tissue cultures are probably the most reliable test but the clinical significance is not always obvious. Synovial fluid cytokine profiles and tissue PCR/NGS show promise for the future.
Utilization of reverse total shoulder arthroplasty (RTSA) has steadily increased since its 2003 introduction in the American market. Although RTSA was originally indicated for elderly, low demand patients, it is now being increasingly used to treat rotator cuff arthropathy, humeral fractures, neoplasms and failed total and hemi shoulder arthroplasty. There is, therefore, a growing interest in bearing surface wear of RTSA polyethylene humeral liners. In the current study, we examined humeral liners retrieved as part of an IRB approved study to determine the amount of bearing surface wear. We hypothesized that wear of the bearing surface by intentional contact with the glenosphere (mode I) would be minor compared to that produced by scapular notching and impingement of the humeral liner (mode II). Twenty-three retrieved humeral liners were retrieved at revision surgery after an average of 1.5 years implantation time. The average age at implantation was 68 years (range 50–85). Shoulders were revised for loosening (7), instability (6), infection (6), pain (2), and other/unknown reasons (2). The liners were scanned using microCT at a resolution of 50 µm and then registered against unworn surfaces to estimate the bearing surface wear depth. The depth of surface penetration due to impingement of the liner with surrounding structures was measured and the location of the deepest penetration was noted. Mode I wear of the bearing surface was detectable for five of the retrieved liners. The penetration depth was 100 µm or less for four of the liners and approximately 250 microns for the fifth liner. It was noted that the liners with discernable mode I wear were those with longer implantation times (average 2.4 years). Material loss and abrasion of the rim due to mode II wear was noted with measurable penetration in 18 of the liners. Mode II wear penetrated to the bearing surface in 11 liners. It was generally noted that volumetric material loss was dominated by mode II wear (Figure 1). In this study of short to medium term retrieved RTSA humeral liners, mode I wear of the bearing surface was a minor source of material loss. Mode II wear due to scapular notching or impingement of the rim was the dominant source of volumetric wear. This is in agreement with a previous study that we have performed on a smaller cohort of seven liners. It is noteworthy that we were able to detect measurable mode I wear for liners with moderate implantation times. The quantity of bearing surface wear that will be seen in long term retrievals remains unknown at this time.
The dichotomy between surgical repair and conservative management of acute Achilles tendon ruptures has been eliminated through appropriate functional management. The orthoses used within functional management however, remains variable. Functional treatment works on the premise that the ankle/hindfoot is positioned in sufficient equinus to allow for early weight-bearing on a ‘shortened’ Achilles tendon. Our aim in this study was to test if 2 common walking orthoses achieved a satisfactory equinus position of the hindfoot. 10 sequentially treated patients with 11 Achilles tendon injuries were assigned either a fixed angle walking boot with wedges (FAWW) or an adjustable external equinus corrected vacuum brace system (EEB). Weight bearing lateral radiographs were obtained in plaster and the orthosis, which were subsequently analysed using a Carestream PACS system. The Mann-Whitney test was used to compare means.Introduction
Methods
Traditional treatment of idiopathic flatfoot in the adult population include calcaneal neck lengthening or fusions. These surgical methods result in abnormal function with significant complication rates. Our prospective study aimed to quantify the functional and radiological outcome of a new technique for spring ligament reconstruction using a hamstring graft, calcaneal osteotomy and medial head of gastrocnemius recession if appropriate. 22 feet were identified from the senior authors flatfoot reconstructions over a 3 year period (Jan 2013 to Dec 2015). 9 feet underwent a spring ligament reconstruction. The control group were 13 feet treated with standard tibialis posterior reconstruction surgery. Follow up ranged from 8 to 49 months. Functional assessment comprised VAS heath and pain scales, EQ-5D and MOXFQ scores. Radiographic analysis was performed for standardised parameters.Introduction
Methods
We aimed to retrospectively identify risk factors for delayed / non-union for first metatarsophalangeal joint fusion. Case notes and radiograph analysis was performed for operations between April 2014 and April 2016 with at least 3 months post-operative follow up. Union was defined as bridging bone across the fusion site on AP and lateral radiographic views with no movement or pain at the MTPJ on examination. If union was not certain, CT scans were performed. All patients operations were performed/supervised by one of three consultant foot surgeons. Surgery was performed through a dorsal approach using the Anchorage compression plate. Blinded pre-operative AP radiographs were analysed for the presence of a severe hallux valgus angle equal or above 40 degrees. Measurement intra-observer reliability was acceptable (95%CI:1.6–2.3 degrees). Smoking and medical conditions associated with non-union underwent univariate analysis for significance.Introduction
Methods
Mechanically assisted crevice corrosion of taper interfaces was raised as a concern in total hip arthroplasty (THA) approximately 20 years ago (Gilbert 1993). In total shoulder replacement, however, comparatively little is known about the prevalence of fretting assisted crevice corrosion or the biomechanical and patient factors that influence this phenomenon. Given the comparatively lower loading experienced in the shoulder compared to the hip, we asked: (1) What is the prevalence of fretting assisted corrosion in modular total shoulder replacements, and (2) What patient and implant factors are associated with corrosion? Modular components were collected from 48 revision shoulder arthroplasties as part of a multi-center, IRB approved retrieval program. For anatomic shoulders, this included 40 humeral heads, 32 stems and four taper adapters from seven manufacturers. For reverse shoulders, there were eight complete sets of retrieved components from three manufacturers. The components were predominantly revised for instability, loosening and pain. Anatomical shoulders were implanted for an average of 3.1 years (st dev 3.8; range 0.1–14.5). Reverse shoulders were implanted for an average of 2.2 years (st dev 0.7; range 1.3–3.3). Modular components were disassembled and examined for taper damage. The modular junctions were scored for fretting corrosion using a semi-quantitative four-point scoring system adapted from Goldberg, et al. (Goldberg, 2002, Higgs 2013). The scoring system criteria was adapted from Goldberg and Higgs which is comprised of a one to four grading system (with one indicating little-to-no fretting/corrosion and four indicating extensive fretting/corrosion). The component alloy composition was determined using the manufacturer's laser markings and verified by x-ray fluorescence. Patient age, gender, hand dominance, alloy, flexural rigidity of the trunnion and taper geometry were assessed independently as predictors for fretting corrosion.INTRODUCTION
METHODS
Retrieval analysis is an important aspect of medical device development. Examination of retrieved devices allows device developers to close the design loop, understand the performance of devices, and validate assumptions made and methods used during preclinical testing. We provide an overview of the implant retrieval analysis performed at the Implant Research Center at Drexel University on reverse total shoulder systems retrieved after short to medium term implantation. We have examined 18 reverse total shoulders, retrieved at revision surgery after short to mid-term implantation (average 1.4 years, maximum 3.3 years). The average age at revision was 71 years old (st dev 11 years). Our evaluations included analysis of glenosphere bearing surface damage, evaluation of tribocorrosion at the modular junctions, visual assessment of polyethylene humeral bearing surface damage, quantitative analysis of polyethylene wear.INTRODUCTION
METHODS
Squamous Cell Carcinoma (SCC) is a rare complication of chronic osteomyelitis (OM), arising in a sinus tract (Marjolin's Ulcer). We routinely send samples for histological analysis for all longstanding sinus tracts in patients with chronic osteomyelitis. We reviewed the clinical features and outcomes of patients with SCC arising from chronic osteomyellitis. A retrospective study was performed of patients with osteomyelitis between January 2004 and December 2014 in a single tertiary referral centre. Clinical notes, microbiology and histo-pathological records were reviewed for patients who had squamous cell carcinoma associated with OM. We treated 9 patients with chronic osteomyelitis related squamous cell carcinoma. The mean age at time of diagnosis was 51 years (range 41–81 years) with 4 females and 5 males. The mean duration of osteomyelitis was 16.5 years (3–30 years) before diagnosis of SCC. SCC arose in osteomyelitis of the ischium in 5 patients, sacrum in 1 patient, femur in 1 patient and tibia in 2 patients. Osteomyelitis was due to pressure ulceration in 7 patients and post-traumatic infection in 2 patients. The histology showed well differentiated SCC in 4 cases and moderately differentiated SCC in 2 cases with invasion. Two patients had SCC with involvement of bone. One patient had metastatic SCC to bowel. All patients had polymicrobial or Gram-negative cultures from microbiology samples. Four patients (57%) in our series died as result of their cancer despite wide resection. The mean survival after diagnosis of SCC was 1.3 years and mean age at time of death was 44.7 years. Two of these patients had ischial disease and were treated with hip disarticulation, hemi-pelvectomy and iliac node clearance. Five patients remain disease free at a mean of 3.4 years (range 0.1 – 7yrs) after excision surgery. One patient in this group underwent a through-hip amputation, one underwent an above knee amputation and one underwent excision of ischium and surrounding sinuses. Of note, all these patients had clear staging scans at time of diagnosis. This case series demonstrates the consequences of an uncommon complication of osteomyelitis. In our series only 3 patients underwent biopsy for suspected SCC due to clinical appearances. The other cases were all identified incidentally after routine histological sampling, demonstrating the importance of this practice.
Chronic osteomyelitis is a challenging clinical problem. Aggressive debridement, bony fixation, obliteration of dead space and vascularised soft tissue coverage with appropriate antimicrobial therapy are essential to successful management of this condition. The gracilis muscle flap is the workhorse flap in our unit for reconstruction of limb osteomyelitis. We describe the experience and use of this flap in our unit over a 3 year period. Clinical records were reviewed from a prospectively-maintained Oxford Free Flap Database and patient notes. All patients who received a free gracilis flap reconstruction as part of the treatment of osteomyelitis between 2011 and 2014 were included in the study. 40 patients received free gracilis flaps; 38/40 for lower limb and 2/40 for upper limb osteomyelitis. Two were myocutaneous flaps, and the remainder were muscle only. The return to theatre rate was 12.5% with a total flap loss rate of 5%. Other flap-specific complications include partial flap loss (2.5%), flap site haematoma (2.5%), donor site haematoma (2.5%) and seroma (2.5%). General complications included pulmonary embolism (2.5%) and death from sepsis (2.5%). All but 2 patients were treated successfully and remain disease free following their initial surgery, with a mean follow up of 12.4 months (range 1–23 months). We have found that the free gracilis muscle flap is effective in the successful treatment of osteomyelitis, with a low complication rate.
Reverse total shoulder replacement is performed for the treatment of rotator cuff arthropathy, massive irreparable cuff tears and failed shoulder hemiarthroplasty with irreparable rotator cuff tears. The aim of this study was to assess the clinical and radiological outcome of single surgeon series of Equinoxe® reverse total shoulder replacement at a district general hospital. Consecutive patients who underwent Equinoxe® reverse total shoulder replacement at our unit from Jun 2008 to Dec 2010 were retrospectively reviewed. Indications for surgery, complications and radiological outcomes were assessed. Oxford shoulder score was used to assess the functional outcome.Introduction
Materials/Methods
Literature in respect to the MRI appearances of surgically confirmed spring ligament pathology is sparse. The authors conducted a retrospective review of MRI examinations comprising 13 patients with surgically proven spring ligament abnormality. Records for operations performed for planovalgus foot deformity with operation notes confirming presence of spring ligament abnormality were obtained for patients treated 2010–11. Of 32 procedures 13 patients (3 male, 10 female) mean age 48.5 (range, 21–86 years) underwent preoperative MRI scanning using a standard musculoskeletal protocol on a T1.5 unit. Scans were retrospectively reviewed by one of the senior authors and consultant musculoskeletal radiologist for pathological findings.Introduction
Methods
No previous studies have attempted to measure parental satisfaction and service quality in regards to paediatric orthopaedic service inpatient care. We performed a prospective observational study to assess parental satisfaction with the level of service provided for paediatric orthopaedic inpatient care in our unit. We employed the validated Swedish parent satisfaction questionnaire to generate parental satisfaction data from 104 paediatric orthopaedic hospital inpatients between August 2009 and May 2010 (49 elective and 55 trauma paediatric orthopaedic admissions, median age range 2–6 years). Questions focused on eight domains of quality: Information on illness, information on routines, accessibility, medical treatment, care processes, staff attitudes, parent participation and staff work environment. Scores generated were a percentage of the maximum achievable for that quality index, for example 100% would correspond to a parent awarding all questions for that index the highest possible score.Introduction
Methods
This pilot study tested the feasibility of a self-determination theory-based communication skills training programme designed to increase physiotherapists' psychological needs supportive behaviour when treating patients with chronic low back pain (CLBP>12 weeks). Both control (Purpose
Methods
Patients were given access to a minimum of two physiotherapy sessions each day, 6 days a week. Typical gait re-education began with the delta rolator frame progressing to walking sticks, stair assessment and finally discharge. Care pathways, operative and medial notes were reviewed for postoperative haemoglobin levels, complications and achievement of functional physiotherapy targets.
Leptin is a major hormonal product of the adipocyte which regulates appetite and reproductive function through its hypothalamic receptors. It has now become clear that leptin receptors are much more widely distributed than just the hypothalamus, and the skeleton has emerged as an important site of action of leptin. The signalling form of the leptin receptor has been found in several cell types including human osteoblasts, rat osteoblasts and human chondrocytes. In vitro we have shown leptin to an anabolic factor, stimulating osteoblast proliferation and inhibiting osteoclastogenesis. Leptin increases bone mass and reduces bone fragility when administered peripherally but has an indirect inhibitory effect on bone mass via the hypothalamus when administered directly into the central nervous system. Data from animal models where there is an absence of either leptin production (ob/ob) or its receptor (db/db) have been contradictory. In this study we compared the bone phenotype of leptin receptor-deficient (db/db) and wild-type (WT) mice. Micro-CT analysis was done on proximal tibiae using a Skyscan 1172 scanner. Db/db mice had significantly reduced trabecular bone volume, trabecular thickness and trabecular number and a higher degree of trabecular separation. Cortical bone was also significantly lower in db/db animals in volume, cross-sectional thickness and perimeter. These results demonstrate that in the absence of leptin signalling there is reduced bone mass indicating that leptin indeed acts in vivo as a bone anabolic factor, mimicking the in vitro results.
Adiponectin, a hormone secreted by adipocytes, regulates energy homeostasis and glucose and lipid metabolism. Plasma levels of adiponectin are negatively correlated with body fat mass. Adiponectin inhibits the formation and activity of osteoclasts and increases the proliferation and differentiation of osteoblasts in vitro. The aim of our study was to determine the bone phenotype of adiponectin knockout mice. Male adiponectin-deficient (Ad-KO) and wild-type (WT) C57BL/6J mice were sacrificed at 8, 14 and 22 weeks of age. Body weights did not differ between Ad-KO and WT mice. We scanned the left proximal tibia using micro-CT at 5μm resolution and analysed bone microarchitecture by 3D analysis. We found significant increases in trabecular bone volume (BV/TV) (15.9±1.63 vs. 12.2±0.72%, p=0.02) and trabecular number (3.20±0.18mm-1 vs. 2.32±0.12mm-1, p=0.0009) in 14-week old Ad-KO mice compared to controls. Similar differences between WT and Ad-KO were present in 8 and 22-week old animals but these did not reach statistical significance. Trabecular thickness was significantly greater (0.053±0.001mm vs. 0.048±0.002mm, p=0.04) in 22-week old Ad-KO mice compared to WT. Ad-KO mice have increased number and volume of trabeculae at 14 weeks of age indicating that the net effect of adiponectin on bone accrual in vivo is inhibitory. These effects are age-dependent. Our data concur with the observations from epidemiological studies in humans that adiponectin negatively correlates with both fat mass and bone mass. Therefore, adiponectin may be a contributor to the link between fat and bone mass.