Thrombotic Prophylaxis in Orthopedic Surgery

In patients undergoing orthopedic surgery, a long-acting anti-thrombotic prophylaxis is usually performed, but is this practice really useful and necessary? Through a multinational trial, sponsored by pharmaceutical industry, the efficacy of a long-term prophylaxis in acute patients has been assessed: everybody has been treated with enoxaparin for 10 days, then all have been randomized to receive further injections of heparin or placebo for 28 further days. Controls have been made when 75% of enrolment was reached (3685 patients) and there have been no differences between enoxaparin and placebo as to thromboembolic events; there has been, instead, a greater tendency to bleeding episodes in the group treated with heparin (0.6% vs. 0.29%). Given these partial results, the trial was early stopped. Analyzing the type of patients participating to the trial, it was seen that they were mostly sick people needing long-term confinement to bed and with other thromboembolic risk factors. The final analysis, on 4995 subjects from both phases of the trial, has shown a lower rate of thromboembolisms in the heparin arm (2.5% vs. 4.0%) and an absolute reduction of 0.8% in symptomatic venous thromboembolisms (almost all deep venous thromboses and not pulmonary embolisms). There was no difference, instead, in overall mortality.

Long-term prophylaxis with heparin certainly implies some problems: according to analyses performed at half trial, it results to be dangerous rather than useful (it increases bleeding episodes without reducing thrombotic ones). Considering only patients with a high risk, instead, a decrease in thrombotic episodes of about 1.5% has been seen, even if the authors of the trial do not specify which is the period of confinement to bed of the various participants, so the conditions of thrombotic risk could have been strongly different from one subject to another. The situation being this, we cannot know yet which are the characteristics of patients doomed to a long-term prophylaxis: no doubt, the indiscriminate administration of heparin to all patients undergoing orthopedic surgery is a practice to be abandoned.

Menopausal Osteoporosis

Despite there is not drugs capable to reduce the risk of fractures of 50%-70% after 6-12 months of treatment, postmenopausal osteoporosis often remains not recognized and consequently not treated, with easily foreseeable consequences. The North American Menopause Society (NAMS), in its declarations in 2010, affirms that all women in post-menopause should be assessed for risk factors associated with osteoporosis, to recognize fracture risk factors, to eliminate possible causes for secondary osteoporosis, to modify risk factors and to choose candidates for pharmacological therapy.In order to better assess fracture risk, now we have the FRAX algorithm at our disposition, while NAMS recommends pharmacological treatment for all patients with clinical (vertebral of hip fractures) or densitometric (T score < -2.5) diagnosis of osteoporosis. Pharmacological therapy is also recommended for those women with a T score between -2.5 and 1.0, but presenting a fracture risk at 10 years higher than 20%, calculated through the FRAX algorithm. In the therapeutical field, denosumab, a human monoclonal antibody inhibiting osteoclast genesis, is added to the series of bisphosphonates. In a wide trial, this drug has reduced the risk of vertebral and hip fractures, through two yearly subcutaneous injections, so it becomes the first-choice drug in patients with a reduced renal function or not tolerating bisphosphonates. As to this last therapy, much is discussed on the need to interrupt it after 3 years: when patients with osteoporosis interrupt the assumption of risedronate after 3 years, in spite of the fact that a drop in bone mineral density and an increase in the markers of bone turnover occur, vertebral fractures occur with an incidence cut by half compared to women using placebo. In women treated with alendronate for 5 years, the following fractures occur with a similar frequency, independently from the continuation or discontinuation of bisphosphonate assumption, even if women treated for 10 years present less fracture risk factors then the ones treated for 5 years.
Diagnostic and therapeutical strategies of osteoporosis have by now been improved and enriched with new and effective drugs. Osteoporosis remains a severe problem in menopausal women (and not only in them), so it is necessary to diagnose and treat it in time, since its worst consequences (fractures) continue to have the very first places in the scale of diseases in old age.

Surgery in Low Back Vertebral Stenosis

In the treatment of pain caused by medullar compression for low back spine stenosis, the interventions of surgical decompression are often used, and in patients presenting listhesis or scoliosis, with consequent vertebral instability, the blocking of 2-3 vertebras is also present. Using the data from Medicare, some researchers have evaluated the frequency of complications of these surgical procedures from 2002 to 2007, a period during which the frequency of vertebral stenosis diagnosis has kept constant; there has been, instead, a clear increase in surgical decompression and vertebral stabilization interventions, even lacking the evidence of spondylolisthesis and scoliosis. In 2007, in a cohort of 32,000 patients, averagely 75 years of age, the rate of major complications has been significantly more frequent in patients treated with complex fusions (front and back accesses, with graft positioning) than in the ones treated with decompression alone (5.2% vs. 2.1%), as well as mortality at 30 days has been higher (0.6% vs. 0.3%). The duration of hospitalizations in case of complex interventions has been three times higher than the ones for decompressions alone.

According to the authors, such an increased frequency in the interventions for vertebral fusion is not justified by a contemporary increase in vertebral diseases, but simply by the performance of newer and newer implantological and orthetic technologies. In the presence of symptomatic vertebral stenosis, it is then necessary to carefully examine surgical therapeutical proposals not to prefer choices directed more by market than by the patient’s real need.

Annual Vitamin D and Fractures

Even if vitamin D administration is widely used to prevent fractures in old women, its usefulness has not got a clear evidence yet. Some Australian researchers, starting from the supposition that its daily
assumption can create some problems for compliance and therapy adhesion,have randomized 2317 women (averagely 76 years of age) with a high fracture risk to receive only one annual dose of vitamin D (500,000 UI) or placebo, for averagely 3-5 years. All women having already taken vitamin D or undergoing other preventive therapies against fractures have been excluded from the trial. Most participants besides took a supplementation of calcium of at least 800 mg. Blood levels of 25-OH-D at the beginning of the trial were about 20 ng/ml. Measured after 1 month, 3 months and 1 year from vitamin D administration, they were
found increased respectively of 2.4 times, of 1.8 times and of twice in treated women compared with the placebo group. During the three year of treatment, the fracture rate has been higher in the group treated with
vitamin than in the placebo group (5 fractures/100 women/year vs. 4; p=0.047). Falls too have been more frequent in the treated group (83 falls/100 women/year vs. 73; p=0.03).The results of this trial are really amazing: the similarity between increase in the number of falls and increase in the fractures would suggest a dose-dependent relation between the administration of vitamin and the fracture risk, but it is not possible to explain such a finding.It is however interesting to note that another trial too, published on Rheumatology (2007; 46:1852), has marked an increase in hip fracture risk after vitamin D supplementation. So, if one wants to give vitamin Din bone prevention, it is better to avoid the practice of annual administration.