Chronic Kidney Disease-Induced Arterial Media Calcification in Rats Prevented by Tissue Non-Specific Alkaline Phosphatase Substrate Supplementation Rather Than Inhibition of the Enzyme

Patients with chronic kidney disease (CKD) suffer from arterial media calcification and a disturbed bone metabolism. Tissue-nonspecific alkaline phosphatase (TNAP) hydrolyzes the calcification inhibitor pyrophosphate (PPi) into inorganic phosphate (Pi) and thereby stimulates arterial media calcification as well as physiological bone mineralization. This study investigates whether the TNAP inhibitor SBI-425, PPi or the combination of both inhibit arterial media calcification in an 0.75% adenine rat model of CKD. Treatments started with the induction of CKD, including (i) rats with normal renal function (control diet) treated with vehicle and CKD rats treated with either (ii) vehicle, (iii) 10 mg/kg/day SBI-425, (iv) 120 µmol/kg/day PPi and (v) 120 µmol/kg/day PPi and 10 mg/kg/day SBI-425. All CKD groups developed a stable chronic renal failure reflected by hyperphosphatemia, hypocalcemia and high serum creatinine levels. CKD induced arterial media calcification and bone metabolic defects. All treatments, except for SBI-425 alone, blocked CKD-related arterial media calcification. More important, SBI-425 alone and in combination with PPi increased osteoid area pointing to a less efficient bone mineralization. Clearly, potential side effects on bone mineralization will need to be assessed in any clinical trial aimed at modifying the Pi/PPi ratio in CKD patients who already suffer from a compromised bone status.

Acute Response of Sclerostin to Whole-body Vibration with Blood Flow Restriction

Blood flow restriction may augment the skeletal response to whole-body vibration. This study used a randomised, crossover design to investigate the acute response of serum sclerostin and bone turnover biomarkers to whole-body vibration with blood flow restriction. Ten healthy males (mean±standard deviation; age: 27±8 years) completed two experimental conditions separated by 7 days: (i) whole-body vibration (10 1-minute bouts of whole-body vibration with 30 s recovery) or (ii) whole-body vibration with lower-body blood flow restriction (10 cycles of 110 mmHg inflation with 30 s deflation during recovery). Fasting blood samples were obtained immediately before and immediately after exercise, then 1 hour, and 24 hours after exercise. Serum samples were analysed for sclerostin, cross-linked C-terminal telopeptide of type I collagen, and bone-specific alkaline phosphatase. There was a significant time × condition interaction for bone-specific alkaline phosphatase (p=0.003); bone-specific alkaline phosphatase values at 24 hours post-exercise were significantly higher following whole-body vibration compared to combined whole-body vibration and blood flow restriction (p=0.028). No significant time × condition interaction occurred for any other outcome measure (p>0.05). These findings suggest that a single session of whole-body vibration combined with blood flow restriction does not significantly affect serum sclerostin or bone turnover biomarkers.

Dose-related effects of extracorporeal shock waves on orthodontic tooth movement in rabbits

The purpose of this animal study is to investigate the quantitative effects of extracorporeal shock waves applied at two different impulses and with two different applicators on orthodontic tooth movement. Thirty-five New Zealand rabbits were randomly divided into five groups (n = 7): the four experimental extracorporeal shock wave groups—focused/500 impulses, focused/1000 impulses, unfocused/500 impulses, and unfocused/1000 impulses—and the control group. Orthodontic tooth movement was achieved by application of reciprocal force between two maxillary incisors. In the experimental groups, animals received 500 or 1000 impulses of extracorporeal shock waves at 0.19 mJ/mm2 with focused or unfocused applicators depending on the group to which they belonged. These experiments were conducted on days 0, 7, and 14. Orthodontic tooth movement was measured with 0.01 mm accuracy at one-week intervals. On days 7 and 21, the bone-specific alkaline phosphatase levels were measured from blood samples. After 21 days, the animals were sacrificed and the area between the two maxillary incisors was stereologically examined. Orthodontic tooth movement in the focused/500 impulses and focused/1000 impulses groups was significantly increased compared to the control group. A significant difference in bone-specific alkaline phosphatase levels between the unfocused/500 impulses and control groups was found at 21st day. Stereological analysis showed that there were significant increases of the formation of new bone, connective tissue, and vessels in the experimental groups. The application of extracorporeal shock waves, especially with a focused applicator, could accelerate orthodontic tooth movement.

Current Approaches in Management of Patients with Hypophosphatasia

he authors present the latest data on the hypophosphatasia (HPP) management in children. Hypophosphatasia is a rare genetic disease caused by deficiency of tissue-specific alkaline phosphatase due to mutation in the ALPL gene. The article covers all the features of epidemiology, etiology and pathogenesis, detailed stages of differential diagnostics. Treatment guidelines for pediatric patients are provided, they are based on the principles of evidence-based medicine. Special attention was given to the only effective method of hypophosphatasia management —enzyme replacement therapy (ERT). This material is the clinical guideline draft for the management of patients with hypophosphatasia prepared by the Union of Pediatricians of Russia and the Association of Medical Geneticists.