Ioannis Polyzois

The effect of β-blockers on bone metabolism as potential drugs under investigation for osteoporosis and fracture healing

Background: β-Adrenergic receptor antagonists (β-blockers) have a well-recognised antihypertensive action that is mediated through a reduction in cardiac output and in the release of renin from the kidneys and inhibition of the action of endogenous catecholamines on β-adrenergic receptors. This class of drugs has been shown to reduce the incidence of cardiovascular disease. Recent evidence suggests that β-blockers may also have an effect on bone structure, metabolism and fracture healing. Objective: This paper reviews in vitro and in vivo data that suggest β-blockers have primarily an anabolic effect on bone metabolism. Results: The sympathetic nervous system has a catabolic effect on bone, and in vitro studies have shown that adrenergic agonists stimulate bone resorption. The β-blocker propranolol has been shown to increase bone formation in ovariectomised female rats. Also, recent observational clinical studies provide evidence to show that β-blockers are associated with reduction in fracture risk in both men and women. Conclusion: Although there are some controversial studies, most research concludes that β-blockers show promise in the treatment of osteoporosis and fracture healing.

Targeting bone morphogenetic protein antagonists: in vitro and in vivo evidence of their role in bone metabolism

Background: Bone morphogenetic proteins (BMPs) and their antagonists are involved in fracture healing. Antagonists regulate BMPs by blocking signal transduction or interfering with transcription factors at the nucleus. Objective: To examine targeting of BMP antagonists to manipulate osteogenesis. Methods: An overview of in vitro and in vivo evidence on effects of BMP antagonists on bone metabolism. Results/conclusion: There is in vitro evidence suggesting that overexpression of noggin and gremlin inhibits osteogenic differentiation, markedly decreases alkaline phosphatase (ALP) levels and impedes R-Smad (1/5/8) phosphorylation in murine cell lines. Knockdown of chordin results in a threefold increase in ALP activity in human mesenchymal stem cells. In vivo data shows that inhibition of noggin leads to increased bone regeneration in mice. Noggin and sclerostin can combine in a mutually inhibitory complex, neutralising their individual inhibitory effects. This allows BMP signalling to proceed to osteoinduction. We highlight the potential for clinical enhancement of bone formation through inhibition of BMP antagonists.

Prostaglandin EP2 and EP4 receptor agonists in bone formation and bone healing: In vivo and in vitro evidence

Background: Using agonists that selectively stimulate PGE2 receptors, the adverse effects that have limited the clinical utility of PGE2 can be avoided and there may be potential for their use as therapeutic agents in the treatment of bone loss in humans. Objective: A comprehensive review of the recent literature on the effect of prostaglandins and their agonists on bone mineral density and fracture healing. Methods: In vitro and in vivo evidence was collected using medical search engines MEDLINE® (1950 to March 2008) and EMBASE (1980 to March 2008) databases. Results/conclusion: EP4 receptors have been identified in human osteoblast cell lines and have also been shown to activate osteoblast directly and osteoclast indirectly via osteoblastic activation. Although there are strong in vitro and in vivo collective data indicating that EP2 receptors may have a role in mediating the anabolic effects of PGE2 on bone, to date no functional EP2 receptors have been identified on human osteoblasts or osteoclasts. This suggests that PGE2 effect on bone formation and resorption in humans may be governed by activation of the EP4 receptor on osteoblasts. Selective EP4 receptor agonists may therefore provide therapeutic potential for systemic use in the treatment of osteoporosis and fracture healing. Further studies need to be carried out in order fully elicit the role of EP2 receptor agonists in fracture healing and bone formation in humans.

Obturator internus pyomyositis in a young adult: a case report and review of the literature

IntroductionThere has been a recent increase in the incidence of myositis worldwide. To this date, myositis has been described almost exclusively in children and adolescents. In most cases the causative agents are Gram-positive bacteria. When it involves muscles around the hip, other differential diagnoses such as septic arthritis and transient synovitis need to be excluded amongst others.Case presentationWe present the case of a 16 year old Caucasian male who suffered from pyomyositis of his left obturator internus muscle. He was pyrexial at 41°C with rigors and severe hip pain, whilst range of motion of his left hip was severely limited. Tenderness over the left pubic bone was significant. After clinical examination and relevant laboratory investigations, it was decided to treat him conservatively with intravenous antibiotics. Blood cultures grew Staphylococcus aureus resistant to amoxicillin and ampicillin. The patient was discharged fifteen days later. At the time of discharge, he was symptom-free.ConclusionThis form of pyomyositis is a rare pyogenic infection, which may be difficult to diagnose and can easily be missed. Therefore, physicians should familiarise themselves with this condition and consider it as a possible differential diagnosis in patients presenting with an acutely painful hip.

Pretibial cyst formation after anterior cruciate ligament reconstruction with poly-L acid screw fixation: a case report presentation and review of the literature.

A pretibial cyst after anterior cruciate ligament (ACL) reconstruction is a rare complication. This report presents a case of a subcutaneous pretibial ganglion with direct communication to the tibial tunnel, after ACL reconstruction with a quadrupled hamstrings tendon autograft, in a 26-year-old Caucasian male. The hamstrings tendon graft was fixed to the tibia using a 9-mm poly-L-lactide interference screw, 4 years earlier. There were no clinical signs of inflammation at the time the cyst appeared. The patient underwent excision of the cyst and curettage of the tibial tunnel. Fibrous tissue and gelatinous material exuded, whereas the screw had completely bioabsorbed. The cyst wall and the content were sent for histological examination (HE). Arthroscopically the graft was probed and found to be intact. HE showed a few giant cells and macrophages. This complication is believed to occur because of a diversion of the biodegrading-bioabsorbing process of the poly-L-lactic acid fixation screw, which led to direct communication between the joint and the pretibial subcutaneous tissue through a fibrous tibial tunnel.

Metastatic malignant melanoma of the conjunctiva: a case report

BackgroundMalignant melanoma of the conjunctiva is an extremely rare non-cutaneous neoplasm with infrequent skeletal metastatic spread.Case presentationWe present the case of a 54 year old female Caucasian patient with osseous metastases originating from a malignant melanoma of her right conjunctiva. Metastatic deposits were identified in the left humeral diaphysis and left tibial metaphysis. Clinical, radiological and scintigraphic evaluation necessitated prompt stabilisation of both long bones. Following reamed intramedullary nailing and post-operative radiotherapy she remains asymptomatic six months post-operatively.ConclusionThis unusual pattern of metastatic spread to the appendicular skeleton of an extremely rare melanomatous lesion requires diagnostic vigilance as well as a multidisciplinary approach for accurate diagnosis, staging and management. Due to the poor prognosis, treatment goals should be directed to palliation of symptoms and prolongation of the quality of life.

Intraoperative anaphylaxis due to gelofusine in a patient undergoing intramedullary nailing of the femur: a case report

BackgroundAlthough uncommon, anaphylaxis due to a colloid plasma expander can occur peri-operativelyCase presentationWe present a case of an intra-operative cardiac arrest in a 72 year old Caucasian male patient who underwent prophylactic intramedullary nailing for a proximal femoral metastasis from prostate cancer. The patient was resuscitated successfully and the procedure was completed uneventfully. Elevated serum tryptase levels confirmed the diagnosis of an anaphylactic reaction and positive allergy skin prick testing identified gelofusine as the causative agent.ConclusionA high index of suspicion, prompt diagnosis and rapid institution of treatment are essential for a safe outcome following such reactions. To our knowledge, this is the first published report of such a severe reaction to gelofusine infusion that occurs during an orthopaedic procedure.

Cowden syndrome. Managing multiple skeletal metastases of different origin: a case report

BackgroundCowden Syndrome is a rare autosomal dominant multiple hamartomatous condition, characterised by both benign and malignant tumours affecting multiple systems.Case presentationWe present a 47-year-old female patient with thigh pain that was diagnosed with Cowden syndrome 20 years ago and developed multiple and different skeletal metastases which became resistant to radio-chemotherapy. A percutaneous plate fixation of the distal femur with an intralesional excision and cementoplasty of the metastasis was performed initially. This was combined with a cemented total hip arthroplasty using an Exeter long revision stem and a cementoplasty of the femoral canal for the proximal lesions.ConclusionA meticulous approach to her complex metastatic disease resulted in successful palliative prophylactic reconstructive surgery that improved her quality of life, allowing her independent pain free walking for 12 months.