The FGF-23/klotho axis and its relationship with phosphorus, calcium, vitamin D, PTH, aldosterone, severity of disease, and outcome in hospitalised foals.

BACKGROUND: Fibroblast growth factor-23 (FGF-23) and klotho are key regulators of vitamin D and parathyroid hormone (PTH) synthesis as well as phosphorus and calcium homeostasis; however, information on the FGF-23/klotho axis in healthy and hospitalised foals is lacking. OBJECTIVES: The aims of this study were to measure serum FGF-23 and klotho concentrations and determine their association with serum phosphorus, total calcium (TCa), vitamin D metabolite [25(OH)D, 1,25(OH)2 D], PTH, and aldosterone concentrations, disease severity, and mortality in hospitalised foals. STUDY DESIGN: Prospective, multicentre, cross-sectional study. METHODS: A total of 91 foals ≤72 h old were classified as hospitalised (n = 81; 58 septic; 23 sick non-septic [SNS]) and healthy (n = 10). Blood samples were collected on admission. Hormone concentrations were determined by immunoassays. RESULTS: Serum FGF-23, PTH, phosphorus, and aldosterone concentrations were higher while klotho, 25(OH)D, 1,25(OH)2 D, and TCa concentrations were lower in septic and SNS compared to healthy foals (P<0.05). In hospitalised and septic foals, increased FGF-23 and aldosterone concentrations were associated with high phosphorus and PTH but not with TCa and vitamin D metabolite concentrations. Hospitalised foals with the highest FGF-23 and lowest klotho concentrations were more likely to die (odds ratio (OR): 3.3; 95% confidence interval (CI): 1.1-10.3 and OR: 3.1; CI: 1.1-8.0, respectively). MAIN LIMITATIONS: Blood gas, ionised calcium, blood culture information not being available for many foals, and use of the sepsis score to classify hospitalised foals. CONCLUSIONS: Imbalances in the FGF-23/klotho axis may contribute to mineral dyshomeostasis and disease progression in critically ill foals. Elevated FGF-23 and reduced klotho, together with high phosphorus and PTH concentrations suggests FGF-23 resistance. FGF-23 and klotho are good markers of disease severity and likelihood of mortality in hospitalised foals. Aldosterone may influence phosphorus and PTH dynamics in hospitalised foals. Routine measurement of phosphorus concentrations in sick foals is recommended.

Animal Models of Bone Metastasis.

Bone is one of the most common sites of cancer metastasis in humans and is a significant source of morbidity and mortality. Bone metastases are considered incurable and result in pain, pathologic fracture, and decreased quality of life. Animal models of skeletal metastases are essential to improve the understanding of the molecular pathways of cancer metastasis and growth in bone and to develop new therapies to inhibit and prevent bone metastases. The ideal animal model should be clinically relevant, reproducible, and representative of human disease. Currently, an ideal model does not exist; however, understanding the strengths and weaknesses of the available models will lead to proper study design and successful cancer research. This review provides an overview of the current in vivo animal models used in the study of skeletal metastases or local tumor invasion into bone and focuses on mammary and prostate cancer, lymphoma, multiple myeloma, head and neck squamous cell carcinoma, and miscellaneous tumors that metastasize to bone.

Combined zoledronic acid and meloxicam reduced bone loss and tumour growth in an orthotopic mouse model of bone-invasive oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is common in cats and humans and invades oral bone. We hypothesized that the cyclooxygenase (COX)-2 inhibitor, meloxicam, with the bisphosphonate, zoledronic acid (ZOL), would inhibit tumour growth, osteolysis and invasion in feline OSCC xenografts in mice. Human and feline OSCC cell lines expressed COX-1 and COX-2 and the SCCF2 cells had increased COX-2 mRNA expression with bone conditioned medium. Luciferase-expressing feline SCCF2Luc cells were injected beneath the perimaxillary gingiva and mice were treated with 0.1 mg kg(-1) ZOL twice weekly, 0.3 mg kg(-1) meloxicam daily, combined ZOL and meloxicam, or vehicle. ZOL inhibited osteoclastic bone resorption at the tumour-bone interface. Meloxicam was more effective than ZOL at reducing xenograft growth but did not affect osteoclastic bone resorption. Although a synergistic effect of combined ZOL and meloxicam was not observed, combination therapy was well-tolerated and may be useful in the clinical management of bone-invasive feline OSCC.

Use of sedation and ropivacaine-morphine epidural for femoral head and neck ostectomy in a dog.

A five-year-old male German shepherd dog presented with traumatic craniodorsal luxation of the right coxofemoral joint with pre-existing moderate hip dysplasia. A femoral head and neck ostectomy was performed. The patient was sedated with acepromazine and morphine administered intramuscularly. A lumbosacral epidural was performed using a combination of morphine and ropivacaine. Intraoperatively, an infusion of medetomidine, morphine, lidocaine, and ketamine was administered intravenously, and oxygen was administered via facemask. Heart rate, respiratory rate and oscillometric arterial blood pressures were monitored. Postoperatively, carprofen was administered once subcutaneously. On the day of hospital discharge, carprofen and tramadol were administered orally every 12 hours. Twenty-one days later, the dog was doing well and the surgical staples were removed. Sedation with acepromazine and morphine, administration of an epidural containing morphine and ropivacaine, and intraoperative sedation with medetomidine, morphine, lidocaine and ketamine were suitable for femoral head and neck ostectomy.

Ulnocarpal arthrodesis for the treatment of radial agenesis in a dog.

Forelimb deformity caused by radial agenesis was diagnosed in a one-year-old Shih Tzu dog. In contrast to most of the previously reported cases of radial agenesis, the humeroulnar joint was inherently stable. The deformity was treated by means of a one-stage ulnocarpal arthrodesis with the application of an eight hole dorsolateral arthrodesis bone plate and autogenous corticocancellous bone graft from the ilial wing. Radiographic evaluation at the eighth and sixteenth post-operative week showed evidence of union of the arthrodesis. At sixteen weeks post-operatively, the dog had much improved limb function. In humans afflicted with radial agenesis, ulnocarpal arthrodesis is used to restore forearm function by minimizing pain and decreasing the magnitude of angular deformity and instability at the level of the ulnocarpal joint. However, to our knowledge, this is the first report of treatment of radial agenesis in the dog by means of a one-stage, ulnocarpal arthrodesis.