Brigitte Florence Uebelhart

Raloxifene Treatment Is Associated With Increased Serum Estradiol and Decreased Bone Remodeling in Healthy Middle‐Aged Men With Low Sex Hormone Levels

In healthy middle‐aged men, raloxifene treatment was associated with increased serum estradiol and decreased biochemical markers of bone turnover in subjects with estradiol levels below a threshold of 101.8 pM.

Risks and benefits of percutaneous vertebroplasty or kyphoplasty in the management of osteoporotic vertebral fractures

Vertebral fracture (VF) is the most common osteoporotic fracture and is associated with high morbidity and mortality. Conservative treatment combining antalgic agents and rest is usually recommended for symptomatic VFs. The aim of this paper is to review the randomized controlled trials comparing the efficacy and safety of percutaneous vertebroplasty (VP) and percutaneous balloon kyphoplasty (KP) versus conservative treatment. VP and KP procedures are associated with an acceptable general safety. Although the case series investigating VP/KP have all shown an outstanding analgesic benefit, randomized controlled studies are rare and have yielded contradictory results. In several of these studies, a short-term analgesic benefit was observed, except in the prospective randomized sham-controlled studies. A long-term analgesic and functional benefit has rarely been noted. Several recent studies have shown that both VP and KP are associated with an increased risk of new VFs. These fractures are mostly VFs adjacent to the procedure, and they occur within a shorter time period than VFs in other locations. The main risk factors include the number of preexisting VFs, the number of VPs/KPs performed, age, decreased bone mineral density, and intradiscal cement leakage. It is therefore important to involve the patients to whom VP/KP is being proposed in the decision-making process. It is also essential to rapidly initiate a specific osteoporosis therapy when a VF occurs (ideally a bone anabolic treatment) so as to reduce the risk of fracture. Randomized controlled studies are necessary in order to better define the profile of patients who likely benefit the most from VP/KP.

Atypical femoral fracture following bisphosphonate treatment in a woman with osteogenesis imperfecta--a case report

A 75-year-old woman presented with acute pain and deformity of her right lower extremity after a fall from standing height. She had suffered from diffuse pain in the right thigh for 4 months, which had begun after some physical exercise with no trauma. Radiographs revealed an atypical fracture of the right femoral shaft, short oblique, with thickening of the entire lateral cortex (9.3 mm as compared to 7.2 mm at the same level on the contralateral nailed femur) and localized cortical reaction at the level of the fracture (Figure). Figure. The atypical fracture of the right femur. The patient had been diagnosed in childhood with a familial form of osteogenesis imperfecta caused by a de novo mutation. Her parents and siblings had no evidence of bone fragility, but 5 of her 6 children had had multiple fractures starting in childhood, associated with typical clinical signs of type-I collagen abnormalities (Rauch and Glorieux 2004). Since childhood, our patient had sustained at least 35 fractures, all of which had healed within a normal period of time. The first to be documented was a femoral fracture at the age of 2, followed by many others involving tibia, radius, ulna, humerus, fingers and toes, bilaterally, until the age of 12. From 12 to 27 years of age there were no fractures reported. At the age of 27 the patient had sustained a wrist fracture, and at the age of 35 she had presented with multiple vertebral compression fractures after falling from a tree. More recent events included a high-energy left midshaft femoral fracture during sports at the age of 62, followed by a fracture of the great toe when she was 71. Because of multiple fractures and osteoporosis (the femoral neck T-score dropped to –2.8 standard deviation when she was 72), she had been administered alendronate (70 mg/week) for the following 3 years, together with calcium and vitamin D supplements (Calcimagon-D3 2 tablets/day). Prior to that, she had been on estrogen replacement therapy (Estraderm day patch) for 13 years. Efficacy of treatment was determined by repeated densitometric evaluations and bone resorption level measurements; the deoxypyridinoline/creatinine ratio was 11 when she was 68 years old, 17 at the age of 72, and 12 one year later (normal range: 8–20). The patient’s femoral fracture was stabilized with an intramedullary nail. Her postoperative course was uneventful and she was discharged 12 days after surgery. At 1-year follow-up, the fracture was well healed. Alendronate was discontinued a few weeks after the atypical fracture.

Effects of bariatric surgery on bone.

Bariatric surgery currently relies on combinations of restrictive and malabsorptive procedures. Early decreases in bone mineral density (BMD) have been reported. However, the accuracy of dual-energy X-ray absorptiometry used to measure BMD can be diminished by the major weight loss, whereas quantitative computed tomography (QCT) measurements are less affected. The nutritional deficiencies induced by mixed bariatric surgery procedures, together with changes in hormones produced by adipocytes and/or the gastrointestinal tract, are often associated with elevations in serum levels of bone resorption markers. Although the data are limited, the incidence of fractures does not seem higher after bariatric surgery than in non-operated obese patients.

Osteoporosis drug treatment: duration and management after discontinuation. A position statement from the SVGO/ASCO.

Antiosteoporotic drugs are recommended in patients with fragility fractures and in patients considered to be at high fracture risk on the basis of clinical risk factors and/or low bone mineral density. As first-line treatment most patients are started with an antiresorptive treatment, i.e. drugs that inhibit osteoclast development and/or function (bisphosphonates, denosumab, oestrogens or selective oestrogen receptor modulators). In the balance between benefits and risks of antiresorptive treatment, uncertainties remain regarding the optimal treatment duration and the management of patients after drug discontinuation. Based on the available evidence, this position statement will focus on the long-term management of osteoporosis therapy, formulating decision criteria for clinical practice.

A randomized double-blind placebo-controlled trial to investigate the effects of nasal calcitonin on bone microarchitecture measured by high-resolution peripheral quantitative computerized tomography in postmenopausal women — Study protocol

BackgroundBone microarchitecture is a significant determinant of bone strength. So far, the assessment of bone microarchitecture has required bone biopsies, limiting its utilization in clinical practice to one single skeletal site. With the advance of high-resolution imaging techniques, non-invasive in vivo measurement of bone microarchitecture has recently become possible. This provides an opportunity to efficiently assess the effects of anti-osteoporotic therapies on bone microarchitecture. We therefore designed a protocol to investigate the effects of nasal salmon calcitonin, an inhibitor of osteoclast activity, on bone microarchitecture in postmenopausal women, comparing weight bearing and non-weight bearing skeletal sites.MethodsOne hundred postmenopausal women will be included in a randomized, placebo-controlled, double-blind trial comparing the effect of nasal salmon calcitonin (200 UI/day) to placebo over two years. Bone microarchitecture at the distal radius and distal tibia will be determined yearly by high-resolution peripheral quantitative computerized tomography (p-QCT) with a voxel size of 82 μm and an irradiation of less than 5 μSv. Serum markers of bone resorption and bone formation will be measured every 6 months. Safety and compliance will be assessed. Primary endpoint is the change in bone microarchitecture; secondary endpoint is the change in markers of bone turnover.HypothesisThe present study should provide new information on the mode of action of nasal calcitonin. We hypothezise that - compared to placebo - calcitonin impacts on microstructural parameters, with a possible difference between weight bearing and non-weight bearing bones.Trial RegistrationClinicalTrials.gov NCT00372099

Hormone replacement therapy: what is the evidence today?

Summary.Based on the most recent studies, it clearly appears that long-term hormone replacement therapy (HRT) prevents fractures but does not improve established coronary artery disease. In addition, HRT leads to a small increase in breast cancer incidence and to a decrease in colorectal cancer incidence. HRT increases the incidence of venous thrombosis, pulmonary embolisms and strokes. As a consequence, HRT can no longer be recommended for primary or secondary prevention of cardiovascular diseases. In addition, it was also demonstrated that HRT was not able to improve cognitive functions and prevent dementia. Therefore regarding daily clinical practice, HRT certainly remains useful to control the symptoms of oestrogen deficiency in recently menopausal patients, but it should definitively no longer be recommended for long-term treatment.Zusammenfassung.Aktuelle Studien zeigen, dass eine längerdauernde Hormon-Substitutionstherapie (HRT) Frakturen verhindern, eine etablierte koronare Herzkrankheit aber nicht verbessern kann. Die HRT führt außerdem zu einer geringen Zunahme der Mammakarzinominzidenz und einer Verminderung der Häufigkeit von kolorektalen Tumoren. Die HRT erhöht des Weiteren die Inzidenz von venösen Thrombosen, Lungenembolien und zerebrovaskulären Insulten. Als Konsequenz kann die HRT weder für die primäre noch für die sekundäre Prophylaxe von kardiovaskulären Erkrankungen empfohlen werden. Zusätzlich wurde gezeigt, dass die HRT kognitive Funktionen nicht verbessern und auch der Entwicklung einer Demenz nicht vorbeugen kann. In der täglichen Praxis bleibt die HRT deshalb der Behandlung von Oestrogenmangelsymptomen bei Patientinnen kurz nach der Menopause vorbehalten, sollte jedoch für Langzeitbehandlung sicher nicht mehr empfohlen werden.