Prospective study of deep vein thrombosis in patients with spinal cord injury not receiving anticoagulant therapy.

STUDY DESIGN: Prospective cross-sectional study. OBJECTIVES: To investigate the timing of deep vein thrombosis (DVT) onset secondary to spinal cord injury without anticoagulant therapies. SETTING: Spinal Cord Injury Center in Hokkaido, Japan. METHODS: Between November 2012 and June 2013, patients with spinal cord injury who were admitted to our hospital within 1 day after the injury and treated surgically within 24 h underwent a neurological examination, leg vein ultrasonography and D-dimer test 1, 3, 7, 14 and 28 days after surgery. All patients received treatment with intermittent pneumatic compression and elastic stockings, but without any anticoagulant. RESULTS: DVT developed in 12 patients (11 men and 1 women), with a mean age of 62.2 years (range, 41-80 years; mean age of total sample, 63.2 years (range, 25-78 years)), all distal to the popliteal vein. DVT occurred more often with a more severe paralysis (66.3%, AIS A and B). The median (± standard error) length of time from the operation to DVT detection was 7.5±2.2 days. The mean D-dimer level upon DVT detection was 14.6±11.8 µg ml(-1), with no significant differences between those who developed DVT and those who did not at any of the time points. CONCLUSION: These results suggest that DVT can develop at the very-acute stage of spinal cord injury and the incidence increases with a more severe paralysis. DVT detection was more reliable with ultrasonography, which should be used with DVT-preventive measures, beginning immediately after the injury, for the management of patients with spinal cord injury.

Changes in the contents of enzymatic immature, mature, and non-enzymatic senescent cross-links of collagen after once-weekly treatment with human parathyroid hormone (1-34) for 18 months contribute to improvement of bone strength in ovariectomized monkeys.

UNLABELLED: Improvements in total content of enzymatic cross-linking, the ratio of hydroxylysine-derived enzymatic cross-links, and non-enzymatic advanced glycation end product cross-link formation from once-weekly administration of hPTH(1-34) for 18 months in OVX cynomolgus monkeys contributed to the improvement of bone strength. INTRODUCTION: Parathyroid hormone (PTH) is used for the treatment of osteoporosis. To elucidate the contribution of material properties to bone strength after once-weekly treatment with hPTH(1-34) in an ovariectomized (OVX) primate model, the content of collagen and enzymatic immature, mature, and non-enzymatic cross-links, collagen maturity, trabecular architecture, and mineralization in vertebrae were simultaneously estimated. METHODS: Adult female cynomolgus monkeys were divided into four groups (n = 18-20 each) as follows: SHAM group, OVX group, and OVX monkeys given once-weekly subcutaneous injections of hPTH(1-34) either at 1.2 or 6.0 µg/kg (low- or high-PTH groups) for 18 months. The content of collagen, enzymatic and non-enzymatic cross-linking pentosidine, collagen maturity, trabecular architecture, mineralization, and cancellous bone strength of vertebrae were analyzed. RESULTS: Low-PTH and high-hPTH treatments increased the content of enzymatic immature and mature cross-links, bone volume (BV/TV), and trabecular thickness, and decreased pentosidine, compared with the OVX group. Stepwise logistic regression analysis revealed that BV/TV, the content of total enzymatic cross-links, and calcium content independently affected ultimate load (model R (2) = 0.748, p < 0.001) and breaking energy (model R (2) = 0.702, p < 0.001). BV/TV was the most powerful and enzymatic cross-link content was the second powerful determinant of both ultimate load and breaking energy. The most powerful determinant of stiffness was the enzymatic cross-link content (model R (2) = 0.270, p < 0.001). CONCLUSION: Once-weekly preventive administration of hPTH(1-34) increased the total contents of immature and mature enzymatic cross-links, which contributed significantly to vertebral cancellous bone strength.

Raloxifene ameliorates detrimental enzymatic and nonenzymatic collagen cross-links and bone strength in rabbits with hyperhomocysteinemia.

UNLABELLED: We demonstrate a reduction in enzymatic divalent immature and trivalent pyridinium cross-links and an increase in the nonenzymatic cross-link, pentosidine (Pen), in rabbits with methionine (Met)-induced hyperhomocysteinemia. Such detrimental cross-link formation in bone was ameliorated by raloxifene (RLX) treatment. INTRODUCTION: Collagen cross-links are determinants of bone quality. Homocysteine (Hcys) interferes with collagen cross-linking. Because RLX is thought to ameliorate bone quality, we investigated whether RLX ameliorated hyperhomocysteinemia-induced cross-link abnormalities using a Met-rich diet rabbit model. METHODS: We divided New Zealand white rabbits into six groups (n = 6 per group): baseline control, sham operation, sham + 1% Met diet, ovariectomy (OVX), 1% Met diet + OVX, OVX + RLX (10 mg/kg/day), and 1% Met diet + OVX + RLX. RLX was administered for 16 weeks. We measured the amount of enzymatic immature and mature pyridinium cross-links and the nonenzymatic cross-link, Pen, and correlated the cross-link content to bone strength. RESULTS: Hcys levels were significantly higher in the Met diet groups than in the normal diet groups. Met-fed rabbits with or without OVX showed a significant reduction of enzymatic cross-links, whereas an increase in Pen was observed in Met-fed rabbits with OVX. The cross-link content of the RLX-treated Met-fed rabbits with OVX was restored to similar levels as the sham group, accompanied by an improvement of bone strength. CONCLUSION: These results demonstrate that hyperhomocysteinemia reduced bone strength via a reduction of enzymatic cross-links and an increase of nonenzymatic cross-links. RLX may ameliorate hyperhomocysteinemia-induced detrimental cross-linking in rabbits with OVX and may improve bone strength via the amelioration of collagen cross-links.