Non-Uremic Calciphylaxis: An Unexpected Complication With Recombinant Human Parathyroid Hormone.

Calciphylaxis is a rare syndrome of calcific microvascular occlusion, whereas non-uremic calciphylaxis (NUC) is a subset of this disease in which renal impairment is not observed. Recombinant human parathyroid hormone (rhPTH) (1-84) is a medication approved for the management of hypocalcemia in patients with hypoparathyroidism. We present a case report of a 38-year-old woman with postoperative hypoparathyroidism treated with rhPTH who subsequently developed calciphylactic lesions on her abdomen. Multidisciplinary interventions included intravenous and intralesional sodium thiosulfate therapy, laboratory monitoring, dermatological wound care, and pain management. Calciphylaxis can rarely be precipitated by rhPTH due to its effect on calcium and phosphorus balance even in the setting of normal renal function. The use of calcium and calcitriol supplementation, complicated by factors such as female sex and obesity, may have contributed in this patient's case. Hence, regular follow-up with tapering off of calcium and calcitriol supplementation is important in patients receiving rhPTH.

Physico-chemical factors controlling the speciation of phosphorus in English and Welsh rivers.

Phosphorus is a finite resource essential for global food production. However, excessive loss to river systems from diffuse sources (typically agricultural) and point sources (e.g. waste water treatment works and industrial effluent) can lead to negative environmental impacts, including changes to diatom and invertebrate community structure. Current environmental quality standards for phosphorus in the UK have been based on reactive phosphorus, which is poorly defined and comprises an unknown proportion of soluble reactive phosphorus and chemically extractable particulate phosphorus. This research assesses the influencing factors that may control soluble reactive phosphorus concentrations in rivers, including dissolved iron, as well as partitioning processes associated with the presence of total suspended solids, and questions the reliability of the assumptions used when setting environmental quality standards. The extensive phosphorus speciation monitoring carried out across a wide geographic area of England and Wales shows that not all phosphorus as measured by the molybdenum blue method is either soluble or necessarily bioavailable, particularly at concentrations in the range in which the Environmental Quality Standard for 'Good' status (typically less than 100 µg P L-1) has been set. Phosphorus speciation can change due to physico-chemical processes which vary spatially and/or temporally, including precipitation with iron and partitioning with suspended solids.

Activation of hedgehog signaling by systemic agonist improves fracture healing in aged mice.

Fracture healing is a complex process of many coordinated biological pathways. This system can go awry resulting in nonunion, which leads to significant patient morbidity. The Hedgehog (Hh) signaling pathway is upregulated in fracture healing. We hypothesized that the Hh signaling pathway can be pharmacologically modulated to positively affect fracture healing. Diaphyseal femur fractures were created in elderly mice (18 months, C57BL/6 females), which have a blunted and delayed healing response compared to younger mice, and were stabilized with intramedullary pins. To activate the Hh pathway we targeted the receptor Smoothened using an agonist (Hh-Ag1.5 [Hh-Ag]) and compared this to a vehicle control. Expression of Hh target genes were significantly increased in the fracture callus of the agonist group compared to controls, indicating pathway activation. Expression of osteogenic and chondrogenic-related genes was greatly upregulated in fracture callus versus intact femora, although Hh agonist treatment did not consistently enhance this response. Blindly graded, radiographic callus healing scores were significantly higher in the Hh-Ag groups at post operative day (POD) 14, indicating earlier callus bridging. On microCT, Hh-Ag treatment led to greater callus volume (+40%) and bone volume (+25%) at POD21. By day 14, callus vascularity, as assessed by 3D microCT angiography vessel volume, was 85% greater in the Hh-Ag group. Finally, mechanical strength of the calluses in the Hh-Ag groups was significantly greater than in the control groups at POD21. In conclusion, systemic administration of a Hh agonist appears to improve the osseous and vascular healing responses in a mouse fracture healing-impaired model. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

Osteoporosis and skeletal fractures.

Osteoporosis affects millions of individuals worldwide, rendering them susceptible to fragility fractures of the spine, hip, and wrist and leading to significant morbidity, mortality, and economic cost. Given the substantial impact of osteoporosis on both patients and the medical community, it is imperative that physicians improve awareness and knowledge of osteoporosis in the setting of low-energy fractures. In this review, we provide information on effective means of preventing fragility fractures and introduce clinicians to issues pertinent to the patient who suffers an osteoporotic fracture. Prevention of fragility fractures centers around adequate mineral nutrition, including daily calcium and vitamin D supplementation, as well as prescription antiresorptive medications such as bisphosphonates or teriparatide therapy in severe cases, both of which have been shown to decrease future fracture risk. Balance and strength training also play important roles in the management of the osteoporotic patient, particularly following a low-energy fracture, and external hip protectors may be useful for certain patients. Kyphoplasty and vertebroplasty are two minimally invasive techniques that show great promise in the treatment of vertebral compression fractures, although questions regarding long-term biomechanical effects still exist. Traditionally, osteoporosis has been underdiagnosed and undertreated following a low-energy fracture in an elderly patient. Although treatment rates may be improving through public health initiatives, the majority of patients with osteoporosis remain inadequately treated. Perioperative intervention programs that focus on patient education about osteoporosis and treatment options lead to significant increases in intervention and treatment. Reducing the risk of skeletal fractures in patients susceptible to osteoporosis involves improved physician education on the risk factors and management of osteoporosis, as well as informing patients on the significance of dual-energy X-ray absorptiometry testing and medical treatment so that they may serve as their own healthcare advocates in this often-undertreated disease.

Improvement in the undertreatment of osteoporosis following hip fracture.

BACKGROUND: Osteoporosis is a common disease characterized by decreased bone mass and increased fracture risk in postmenopausal women and the elderly. Hip fractures are among the most common consequences of osteoporosis and unfortunately usually occur late in the course of the disease. When a patient is admitted to the hospital with a fragility hip fracture, a unique opportunity for diagnosis and treatment presents itself. Fortunately, several medications have proven to be effective in lowering the risk of future fractures. The purposes of the present study were to test the hypothesis that most fragility hip fractures go untreated and to determine whether educational efforts to raise physician awareness have led to an improvement in osteoporosis treatment rates. METHODS: A retrospective cohort study was performed with use of the patient databases at two university medical centers and one university-affiliated community hospital. The charts of 300 randomly selected patients were sorted with use of ICD-9 (International Classification of Diseases, Ninth Revision) codes for femoral neck fractures. There were 100 patients from each center, with twenty-five patients from each year between 1997 and 2000. The admitting diagnosis, mechanism of injury, admission medications, procedures performed during hospitalization, and discharge medications were then extracted and analyzed. During this period, the National Osteoporosis Foundation established guiding principles for the treatment of fragility fractures. RESULTS: Of the seventy-five patients from all centers for each year from 1997 to 2000, 11%, 13%, 24%, and 29%, respectively, were discharged with a prescription for some medication targeting osteopenia, either supplemental calcium or an antiosteoporotic medication (estrogen, calcitonin, a bisphosphonate, or raloxifene). A trended chi-square analysis of this increase revealed a p value of <0.001, indicating that this improvement in treatment was unlikely due to chance alone. Fifty-eight (19.3%) of the 300 patients in the study received a prescription at the time of discharge. However, forty of these patients (13.3% of the overall group) received calcium and only eighteen (6.0% of the overall group) received a medication to actively prevent bone resorption and treat osteoporosis. In addition, no patient underwent a bone density scan while in the hospital. CONCLUSIONS: Elderly patients and postmenopausal women who are admitted to the hospital and diagnosed with a low-energy femoral neck fracture have been undertreated for osteoporosis. However, over the four years of the present study, there was a significant increase in the rate of treatment. It is hoped that treatment rates will continue to increase in the future with continued educational efforts.