Treatment with Fluoride or Bisphosphonates Prevents Bone Loss Associated with Colitis in the Rat

Idiopathic inflammatory bowel disease (IBD) is associated with osteoporosis in over 30% of cases. We have previously shown that 2,4,6-trinitrobenzenesulphonic acid (TNBS)-induced colitis in rats is associated with considerable bone loss. In the current study we tested the ability of sodium fluoride (NaF) or the bisphosphonate pamidronate to prevent the bone loss associated with TNBS-induced colitis in 22-week-old male Wistar rats. As previously found, there was a 43% decrease in cancellous bone volume in rats with TNBS-induced colitis after 4 weeks. This was associated with marked suppression of the bone formation rate to less than 25% of control animals. Treatment with NaF had no effect on the severity of colitis, but the bone volume and bone formation rate were increased to levels indistinguishable from those of control animals. In animals treated with pamidronate, cancellous bone volume was also restored to that of control animals despite persistence of the colitis. In these animals there was marked suppression of bone formation, associated with suppression of bone resorption. This data shows the bone loss associated with colitis may be prevented by treatment with NaF or bisphosphonates without requiring improvement in severity of the colitis. Received: 20 May 1999 / Accepted: 19 June 2000 / Online publication: 22 September 2000     

Bisphosphonates in the Treatment of Thalassemia-Induced Osteoporosis

The aim of our randomized, placebo-controlled study was to investigate the effects of 2 years’ daily oral administration of alendronate or intramuscular administration of clodronate every 10 days, on bone remodeling parameters and bone mineral density (BMD), safety and tolerability in a group of osteoporotic thalassemic patients. Twenty-five young patients (mean age 26.6 ± 7.1 years) with beta-thalassemia major were randomly divided to receive placebo or 100 mg of clodronate intramuscularly every 10 days or 10 mg of alendronate per os daily. All patients took 500 mg of elemental calcium and 400 IU cholecalciferol in the evening at meal time. After 2 years, pyridinium crosslinks, which are bone resorption markers, did not differ significantly from baseline values in the placebo group, whereas they had decreased significantly in the clodronate and alendronate groups. Osteocalcin, a bone formation marker, did not change significantly in the placebo group, whereas it decreased slightly, but not significantly, in the clodronate and alendronate groups after 12 and 24 months. At the end of the study, the lumbar spine BMD had decreased significantly in the placebo group; it did not change significantly in the clodronate group; in the alendronate group it had increased but not significantly, whereas the increase was significant with respect to the placebo group. Femoral neck BMD decreased significantly in the placebo group; it did not change significantly in the clodronate group, but increased significantly in the alendronate group. No relevant side effects were recorded during our study. In conclusion, in patients with thalassemia-induced osteoporosis, the daily administration of alendronate significantly increases BMD, the most important predictor of the risk of fracture at several sites. Clodronate treatment at our dosage is ineffective in this pathology in spite of the good compliance of patients. Received: 13 August 2001 / Accepted: 19 February 2002     

Alendronate for the Treatment of Osteoporosis in Men

The incidence of osteoporotic fracture in males is approximately one-third of that observed in women, but information on specific therapies is almost exclusively limited to bisphosphonate alendronate. The most important study with this compound included 241 men, randomized to receive either alendronate 10 mg/day or placebo. In another study 134 men were given either 10 mg alendronate or alfacalcidiol 1 microg/day. After 24 months, the treatment with alendronate bone mineral density (BMD) significantly increased in both studies by 7-10% at the lumbar spine and by 2.5-5.2% at the femoral neck. These changes were associated with decreases in vertebral fracture rate and in stature loss, both statistically significant when the data of the two trials were meta-analysed. The BMD changes after alendronate therapy were comparable to those observed in postmenopausal osteoporosis. This was confirmed in a trial specifically designed to compare alendronate efficacy in men and postmenopausal women with either primary or secondary osteoporosis. Gender-comparative efficacy data can also be inferred from clinical trials in glucocorticoid-induced osteoporosis of alendronate, risedronate, and etidronate, carried out in both women and men. By combining the results of all these trials, bisphosphonate efficacy in terms of both BMD changes and fracture incidence appears to be moderate in premenopausal women but quite obvious and comparable in males and postmenopausal women.     

The Removal of Post-sclerotherapy Pigmentation following Sclerotherapy Alone or in Combination with Crossectomy

Background

Sclerotherapy is a widely used method for the obliteration of blood vessels. Hyperpigmentation is a frequent complication that results from haemosiderin (FeO) accumulation. Hyperpigmentation and changes in the skin can be observed with ultrasound.

Objective

The aim of this study was to evaluate the efficacy of hyperpigmentation elimination using an intense pulse light generator (IPL) equipped with radio waves (RF) under ultrasonography (US) control.

Methods

Twenty-one women with permanent hyperpigmentation (after sclerotherapy or crossectomy combined with sclerotherapy) underwent a hyperpigmentation eliminating therapy with the use of IPL + RF and were monitored by using US. The thicknesses of the dermis and the subcutaneous tissue as well as the echogenicities of each layer were assessed.

Results

As a result of the therapy, a complete regression of hyperpigmentation was achieved in 90.48% of the women, and in 9.52% of the women, the therapy led to a reduction in hyperpigmentation but did not cause its complete disappearance. An increase in dermal echogenicity and a decrease in subcutaneous tissue echogenicity were observed, but there was no change in their thicknesses. After the therapy, the ultrasound images of areas of previous hyperpigmentation corresponded with images that were characteristic of healthy skin.

Conclusion

IPL + RF therapy is effective for eliminating permanent skin hyperpigmentation after sclerotherapy. US is also useful in this therapeutic method.     

Minimum Alveolar Concentration-Awake of Xenon Alone and in Combination with Isoflurane or Sevoflurane

Background: The minimum alveolar concentration (MAC)-awake is a traditional index of hypnotic potency of an inhalational anesthetic. The MAC-awake of xenon, an inert gas with anesthetic properties (MAC = 71%), has not been determined. It is also unknown how xenon interacts with isoflurane or sevoflurane on the MAC-awake.

Methods: In the first part of the study, 90 female patients received xenon, nitrous oxide (N2O), isoflurane, or sevoflurane supplemented with epidural anesthesia (n = 36 for xenon and n = 18 per group for other anesthetics). In the second part, 72 additional patients received either xenon or N2O combined with the 0.5 times MAC-awake concentration of isoflurane or sevoflurane (0.2% and 0.3%, respectively, based on the results of the first part; n = 18 per group). During emergence, the concentration of an assigned anesthetic (xenon or N2O only in the second part) was decreased in 0.1 MAC decrements every 15 min from 0.8 MAC or from 70% in the case of N2O until the patient followed the command to either open her eyes or to squeeze and release the investigator's hand. The concentration midway between the value permitting the first response to command and that just preventing it was defined as the MAC-awake.

Results: The MAC-awake were as follows: xenon, 32.6 +/- 6.1% (mean +/- SD) or 0.46 +/- 0.09 MAC; N2O, 63.3 +/- 7.1% (0.61 +/- 0.07 MAC); isoflurane, 0.40 +/- 0.07% (0.35 +/- 0.06 MAC); and sevoflurane, 0.59 +/- 0.10% (0.35 +/- 0.06 MAC). Addition of the 0.5 MAC-awake concentrations of isoflurane and sevoflurane reduced the MAC-awake of xenon to 0.50 +/- 0.15 and 0.51 +/- 0.16 times its MAC-awake as a sole agent, but that of N2O to the values significantly greater than 0.5 times its MAC-awake as a sole agent (0.68 +/- 0.12 and 0.66 +/- 0.14 times MAC-awake;P < 0.01, analysis of variance and Dunnett's test).     

Idiopathic Osteoporosis in Men

Over the last decade, the increasingly significant problem of osteoporosis in men has begun to receive much more attention than in the past. In particular, recent observations from large scale population studies in males led to an advance in the understanding of morphologic basis of growth, maintenance and loss of bone in men, as well as new insights about the pathophysiology and treatment of this disorder. While fracture risk consistently increases after age 65 in men (with up to 50 % of cases due to secondary etiologies), osteoporosis and fractures may also occur in young or middle aged males in the absence of an identifiable etiology. For this category (so called idiopathic osteoporosis), there are still major gaps in knowledge, particularly concerning the etiology and the clinical management. This article provides a summary of recent developments in the acquisition and maintenance of bone strength in men, as well as new insights about the pathogenesis, diagnosis, and treatment of idiopathic osteoporosis.     

Secondary Causes of Osteoporosis in Men

Important underlying causes of osteoporotic fracture in men include glucocorticoid therapy, low body weight, and reduced physical activity. Tobacco and alcohol use have been consistently identified as risk factors for vertebral fracture but there is less evidence that they contribute to hip fracture. Clinically overt hypogonadism is a strong risk factor for osteoporosis in men; however, the role of more subtle subclinical changes, as defined by biochemical criteria, remains to be established. The high comorbidity associated with osteoporosis, particularly in elderly men, contributes to fracture risk both through effects on bone mass and risk of falling. The management of osteoporosis in men includes diagnosis of and, where possible, correction of underlying contributory causes. Evidence from recent randomized controlled trials indicates that bisphosphonates are effective in the prevention of glucocorticoid-induced osteoporosis in men but the optimal criteria for selection of individuals for treatment requires further study.     

Alendronate Treatment in Men With Primary Osteoporosis: A Three-Year Longitudinal Study

Bisphosphonates have been widely used in the treatment of osteoporosis in women, whereas until now there have been few data on their use in men. The aim of this study was to evaluate the effect of a 3-year alendronate treatment on bone mineral density (BMD) and quantitative ultrasound (QUS) in men with primary osteoporosis. We studied 77 osteoporotic men (aged 57.1 ± 10.8 yrs) who completed a 3-year treatment with alendronate (10 mg/day) plus calcium (1000 mg/day) (n = 39), or calcium alone (n = 38). At baseline and at a 12-month interval, we measured BMD at the lumbar spine and femur (femoral neck and total hip) by DXA (Hologic) and speed of sound (SOS), broadband ultrasound attenuation (BUA) and Stiffness (S) at the os calcis by Achilles plus (Lunar). Alendronate treatment had significantly increased lumbar spine BMD by 4.2% at year 1, by 6.3% at year 2, and 8.8% at year 3. BMD at the femoral neck and total hip had increased by 2.1% and 1.6% at year 1, by 3.2% and 2.9% at year 2, and by 4.2% and 3.9% at year 3, respectively. BUA and Stiffness showed a significant increase in the alendronate-treated group at year 2 (3.2% and 4.9%, respectively) and at year 3 (3.8% and 6%, respectively). BMD at the lumbar spine showed the best longitudinal sensitivity whereas longitudinal sensitivity of both QUS at the heel and femur BMD were similar. In conclusion, this study confirms that alendronate represents an important therapeutic advance in the management of male osteoporosis. BMD at the lumbar spine appears to be the best method for monitoring the effect of alendronate on bone mass in osteoporotic men.     

Risk Factors for Proximal Femur Osteoporosis in Men Aged 50 Years or Older

The objective of this study was to analyze the risk factors for osteoporosis in 325 volunteer men aged 50 years or older. Participants completed questionnaires including demographic and social information, personal medical history, maternal and paternal history of bone fracture after the age of 50 years, smoking habit, alcoholic beverage consumption, calcium intake and present and past physical activities. The individuals were submitted to bone densitometry of the femoral neck and to anthropometric measurements. The χ² test and multiple logistic regression were used to evaluate the association between the independent variables and the presence of osteoporosis. We concluded that the independent risk factors for osteoporosis were body mass index, present practice of physical/leisure activity (last 12 months), age, present and past smoking habit, no current thiazide diuretic use, white race and maternal history of fracture after the age of 50 years. Received: 16 January 2001 / Accepted: 10 May 2001     

Treatment of Postmenopausal Women with Osteoporosis or Low Bone Density with Raloxifene

Raloxifene, a selective estrogen receptor modulator (SERM), has been shown to improved bone mineral density (BMD) and serum lipid profiles in healthy postmenopausal women. The objective of this study was to examine the effects of raloxifene on BMD, biochemical markers of bone metabolism and serum lipids in postmenopausal women with low bone density or osteoporosis. This Phase II, multicenter, 24-month, double-masked study assessed the efficacy and safety of raloxifene in 129 postmenopausal women (mean age ± SD: 60.2 ± 6.7 years) with osteoporosis or low bone density (baseline mean lumbar spine BMD T-score: −2.8). Women were randomly assigned to one of three treatment groups: placebo, 60 mg/day raloxifene-HCl (RLX 60) or 150 mg/day raloxifene-HCl (RLX 150) and concomitantly received 1000 mg/day calcium and 300 U/day vitamin D₃. At 24 months, BMD was significantly increased in the lumbar spine (+3.2%), femoral neck (+2.1%), trochanter (+2.7%) and total hip (+1.6%) in the RLX 60 group compared with the placebo group (p<0.05). The RLX 150 group had increases in BMD similar to those observed with RLX 60. A greater percentage of raloxifene-treated patients, compared with those receiving placebo, had increased BMD (p<0.05). Serum bone-specific alkaline phosphatase activity, serum osteocalcin, and urinary type I collagen:creatinine ratio were significantly decreased in the RLX-treated groups, compared with the placebo group (p<0.01). RLX 60 treatment significantly decreased serum levels of triglycerides, and total- and LDL-cholesterol levels (p<0.01). The rates of patient discontinuation and adverse events were not significantly different among groups. In this study, raloxifene increased bone density, decreased bone turnover, and improved the serum lipid profile with minimal adverse events, and may be a safe and effective treatment for postmenopausal women with osteoporosis or low bone density. Received: 26 December 1998 / Accepted: 31 March 1999     

Locking Plate Alone or in Combination with Cannulated Screws for Hoffa Fractures: A Retrospective Study

ObjectiveTo determine the efficacy of distal femur condyle locking plate (DFCLP) alone or in combination with cannulated screws for Hoffa fractures.MethodsIn this study, between May 2014 and February 2019, 13 patients between 26 and 64 years with isolated Hoffa fractures were enrolled during the study period and retrospectively analyzed. All patients underwent open reduction and internal fixation by DFCLP alone or in combination with cannulated screws followed by early active rehabilitation postoperatively. The primary outcome was evaluated using range of movement (ROM), Knee Society Score (KSS), International Knee Documentation Committee (IKDC) scoring system, and the fracture healing time of the patients during the 24‐month follow‐up period. Postoperative complications were also used to assess the patients’ conditions.ResultsA total of 13 patients completed the 24‐month follow‐up assessment and achieved bone re‐union at Hoffa fracture sites. The average follow‐up period was 24.5 months (ranging from 24 to 28 months). Six patients were treated by DFCLP in combination with cannulated screws and the remaining seven patients were treated by DFCLP alone. The mean ROM was determined as 119° (ranging from 100° to 130°). The mean KSS score was 87.9 (ranging from 80 to 92 points), with 11 patients evaluated as excellent, two as good, and zero bad cases. The mean IKDC score was 84.2 (ranging from 74.7 to 89.7 points), with 10 evaluated as excellent, three as good, and zero bad cases. The mean IKDC score was 83.3 for patients with medial Hoffa fractures and 84.4 for those with lateral Hoffa fractures. The average time to healing was 3.5 months (ranging from 3 to 4 months), and at month 3, the fracture healing was evident in seven patients (54%), and at month 4, fracture healing was seen in six patients (46%). It is worth mentioning that two patients suffered from knee joint stiffness and osteoarthritis during the 24 months follow‐up. Eleven patients (84.6%) achieved satisfactory knee joint function through early postoperative rehabilitation.ConclusionIn patients with Hoffa fractures, treatment with DFCLP alone or in combination with cannulated screws followed by early active rehabilitation resulted in great stability and satisfactory functional outcomes after 24 months. Our findings may provide surgeons with a new way to treat Hoffa fractures.     

Biodegradable Carmustine Wafers (Gliadel) Alone or in Combination with Chemoradiotherapy: The French Experience

Background

Carmustine-releasing wafers (Gliadel^®) have been available and reimbursed in France since 2005.

Methods

A retrospective multicenter study was conducted in 26 French Departments of Neurosurgery to analyze practices of French neurosurgeons using Gliadel, compare the adverse effects and survival with those of previous phase III trials, and assess survival in patients with newly diagnosed malignant gliomas (MG) receiving Gliadel plus radiochemotherapy with temozolomide (TMZ). A total of 163 patients who received Gliadel for MG were included in this study: 83 (51%) with newly diagnosed MG and 80 (49%) with recurrent MG. In the newly diagnosed group, 51.8% of patients received radiochemotherapy with TMZ.

Results

Adverse events (AEs) emerged in 44.6% of the population, including 6% with septic abscess. The AE rate was not statistically correlated with adjuvant use of TMZ. For the newly diagnosed group, median survival was 17 months. Total or subtotal resection appeared to have a great impact on survival (P = 0.016), as did treatment with adjuvant radiotherapy (P = 0.004).For the group with recurrent MG, median survival was 7 months. Total or subtotal resection excision appeared to have a great impact on survival (P = 0.002), as did preoperative Karnowsky Scale (PO-KPS) (P = 0.012).

Conclusions

Survival rates for newly diagnosed patients were better than those reported in previous phase III trials. The combination of Gliadel and radiochemotherapy with TMZ was well tolerated and appeared to increase survival without increasing AEs.

     

Osteoporosis in Men: Pathophysiology and treatment

Osteoporosis has long been long considered a disease of the aging female skeleton. However, it is now clear that men are also at risk for this disorder. Epidemiologic studies have confirmed that osteoporotic fractures in men are an increasing public health problem, in part due to increased longevity and increased public awareness. Recent large-scale population studies in men have led to advances in our understanding of bone fragility and its treatment in men. This article reviews what is known about the factors in men that lead to acquisition, maintenance, and loss of bone, as well as new insights into causes, pathogenesis, and treatment of osteoporosis in men.     

Diagnosis of Osteoporosis and Fracture Threshold in Men

This review examines the hypothesis that there are gender differences in the relationship between bone mineral density (BMD) and fracture risk. Prospective studies of spine and hip fracture risk drawn from population samples suggest that the fracture risk increases as BMD decreases in men in the same way as that described in women. Moreover, for any given BMD at the spine, heel, or proximal femur the risk in men is similar to that in women. Although data are limited, prior fragility fractures increase subsequent fracture risks in both men and women. These studies suggest that the same BMD criteria used to diagnose osteoporosis in women can be applied to men.