Helmut W. Minne

Randomized Trial of the Effects of Risedronate on Vertebral Fractures in Women with Established Postmenopausal Osteoporosis

Abstract: The purpose of this randomized, double-masked, placebo-controlled study was to determine the efficacy and safety of risedronate in the prevention of vertebral fractures in postmenopausal women with established osteoporosis. The study was conducted at 80 study centers in Europe and Australia. Postmenopausal women (n= 1226) with two or more prevalent vertebral fractures received risedronate 2.5 or 5 mg/day or placebo; all subjects also received elemental calcium 1000 mg/day, and up to 500 IU/day vitamin D if baseline levels were low. The study duration was 3 years; however, the 2.5 mg group was discontinued by protocol amendment after 2 years. Lateral spinal radiographs were taken annually for assessment of vertebral fractures, and bone mineral density was measured by dual-energy X-ray absorptiometry at 6-month intervals. Risedronate 5 mg reduced the risk of new vertebral fractures by 49% over 3 years compared with control (p<0.001). A significant reduction of 61% was seen within the first year (p= 0.001). The fracture reduction with risedronate 2.5 mg was similar to that in the 5 mg group over 2 years. The risk of nonvertebral fractures was reduced by 33% compared with control over 3 years (p= 0.06). Risedronate significantly increased bone mineral density at the spine and hip within 6 months. The adverse-event profile of risedronate, including gastrointestinal adverse events, was similar to that of control. Risedronate 5 mg provides effective and well-tolerated therapy for severe postmenopausal osteoporosis, reducing the incidence of vertebral fractures and improving bone density in women with established disease.

Effects of a short-term vitamin D and calcium supplementation on body sway and secondary hyperparathyroidism in elderly women

Long‐term vitamin D and calcium supplementation is effective in reducing nonvertebral fractures in elderly people. Increased bone fragility caused by secondary hyperparathyroidism (sHPT) and impaired balance are known risk factors for hip fractures. The hypothesis is that short‐term therapy with calcium and vitamin D may improve body sway as well as sHPT more effectively than calcium monotherapy. The effects of 8 weeks of supplementation with vitamin D (cholecalciferol) and calcium on body sway and biochemical measures of bone metabolism were measured. The sample consisted of 148 women (mean [±SD] age, 74 ± 1 years) with a 25‐hydroxycholecalciferol level below 50 nmol/liter. They received either 1200 mg of calcium plus 800 IU of vitamin D or 1200 mg of calcium per day. We measured intact parathyroid hormone (PTH), markers of bone turnover, and body sway before and after treatment. Falls and fractures among the participants were followed over a 1‐year period. Compared with calcium mono, supplementation with vitamin D and calcium resulted in an increase in serum 25‐hydroxyvitamin D of 72% (p < 0.0001), a decrease in the serum PTH of 18% (p = 0.0432), and a decrease in body sway of 9% (p = 0.0435). The mean number of falls per subject during a 1‐year follow‐up period was 0.45 for the calcium mono group and 0.24 for the calcium and vitamin D group (p = 0.0346). Short‐term supplementation with vitamin D and calcium improves sHPT and body sway and therefore may prevent falls and subsequent nonvertebral fractures in elderly women.

Reduced Pulmonary Function in Patients with Spinal Osteoporotic Fractures

Abstract: Vertebral deformation in spinal osteoporosis results in spinal and thoracic deformation, causing pain, disability and an overall decrease in quality of life. We sought to determine whether thoracic spinal deformation may lead to impaired pulmonary function. We studied expiratory relaxed vital capacity (VC) and forced expiratory volume in 1 s (FEV1) in 34 patients with spinal osteoporotic fractures and 51 patients with chronic low back pain (CLBP) due to reasons other than osteoporosis. Measurements of pulmonary function tests were calculated as a percentage of the normal range adjusting for age, sex, and height using the equations for normal values of the EKGS (Europäische Gesellschaft für Kohle und Stahl). Severity of osteoporosis was determined by calculation of the spine deformity index (SDI-total and SDI-anterior) on lateral radiographs of the spine and clinical measures of body stature (height reduction, distance from lowest ribs to iliac crest and distance from the occiput to the wall). Patients with osteoporosis had a lower vital capacity (%VC of the reference value) than patients with CLBP. The differences were more prominent (p<0.05) when the previous body height, at age 25 years, was used as reference for calculation of VC (mean ± SD: 93.6%± 15.3% in patients with osteoporosis v 105.6%± 15.1% in patients with CLBP). FEV1 was significantly (p<0.05) lower in patients with osteoporosis when previous body height was considered, in comparison with patients with CLBP (mean ± SD: 85.0%± 14.2% in patients with osteoporosis v 92.4%± 13.6% in patients with CLBP). In patients with osteoporosis VC (standardized on previous body height) was significantly negatively correlated with SDI-anterior (r=–0.4, p<0.03). Furthermore, VC standardized on previous body height showed a weak but significant negative correlation with some clinical measures of osteoporosis (height reduction vs %VC: r=–0.34, p<0.05; distance from the lowest ribs to iliac crest vs %VC: r= 0.35, p<0.04). In conclusion, we found that pulmonary function is significantly diminished in patients with spinal osteoporotic fractures as compared with CLBP patients without evidence of manifest osteoporosis. Reduction of pulmonary function is correlated significantly with clinical and radiological measures of severity of spinal deformation due to osteoporotic fractures.

Vitamin D and Muscle Function

The aim of this review is to summarize current knowledge on the relation between vitamin D and muscle function. Molecular mechanisms of vitamin D action on muscle tissue have been known for many years and include genomic and non-genomic effects. Genomic effects are initiated by binding of 1,25-dihydroxyvitamin D3 (1,25(OH)2D) to its nuclear receptor, which results in changes in gene transcription of messenger RNA and subsequent protein synthesis. Non-genomic effects of vitamin D are rapid and mediated through a membrane-bound vitamin D receptor (VDR). Genetic variations in the VDR and the importance of VDR polymorphisms in the development of osteoporosis are still a matter of controversy and debate. Most recently, VDR polymorphisms have been described to affect muscle function. The skin has an enormous capacity for vitamin D production and supplies the body with 80–100% of its requirements of vitamin D. Age, latitude, time of day, season of the year and pigmentation can dramatically affect the production of vitamin D in the skin. Hypovitaminosis D is a common feature in elderly people living in northern latitudes and skin coverage has been established as an important factor leading to vitamin D deficiency. A serum 25-hydroxyvitamin D level below 50 nmol/l has been associated with increased body sway and a level below 30 nmol/l with decreased muscle strength. Changes in gait, difficulties in rising from a chair, inability to ascend stairs and diffuse muscle pain are the main clinical symptoms in osteomalacic myopathy. Calcium and vitamin D supplements together might improve neuromuscular function in elderly persons who are deficient in calcium and vitamin D. Thus 800 IU of cholecalciferol in combination with 1200 mg of elemental calcium reduces hip fractures and other non-vertebral fractures and should generally be recommended in individuals who are deficient in calcium and vitamin D. Given the strong interdependency of vitamin D deficiency, low serum calcium and high levels of parathyroid hormone, however, it is difficult to identify exact mechanisms of action.

A study of complaints and their relation to vertebral destruction in patients with osteoporosis

Patients with spinal osteoporosis suffer from vertebral deformation, loss of height and back pain, as well as from functional limitations and alterations of mood. So far little is known about the extent of these clinical symptoms at all and whether they are related in a predictable manner to the fractures or damages of bone structure. In the present study we investigated the relation between vertebral deformation and clinical symptoms in 70 patients with osteoporosis. Clinical data like pain, functional limitations and parameters of mood were examined by a standardized questionnaire. The numbers of vertebral fractures were determined, and the vertebral destruction was quantified using the Spine Deformity Index (SDI). The symptoms and functional limitations were graded and correlated to the SDI and the number of fractures. Our results underline a relation between the extent of vertebral deformation and the reduction in quality of life by pain, functional limitations and alterations of mood. This relationship was absent or less evident, if the number of fractures was taken into account. Besides the difficulties concerning the grading and quantification of clinical symptoms and outcome of disease, our study revealed that there is a causal relation between the extent of vertebral destruction measured by the SDI and the extent of these clinical parameters.

Clinical Grading of Spinal Osteoporosis: Quality of Life Components and Spinal Deformity in Women with Chronic Low Back Pain and Women with Vertebral Osteoporosis

Clinical consequences of osteoporotic vertebral fractures, such as back pain, functional limitations, and impairment of mood, are often cited as justification for prevention and therapy. But these symptoms are poorly characterized, and a clinical grading system is not available. The aim of this study was to compare clinical measures for spinal deformation and quality of life components between patients with osteoporosis and patients with chronic low back pain (CLBP) and to determine the relationship between spinal deformation and quality of life components. A total of 130 female patients (63 osteoporotic patients, 65 ± 7.9 years, and 77 CLBP patients, 56 ± 6.5 years) had a standardized interview on quality of life components (pain, activities of daily life, mood) and clinical measures of spinal deformation (height reduction [HR], distance from occiput to wall [DOW], and distance from iliac crest to ribs [DIR]). Spinal X‐rays were reviewed in all patients for the evidence of vertebral fractures. In osteoporotic patients, vertebral deformity was quantified by the spine deformity index (SDI) on X‐rays. It was assessed whether subgroups could be identified by a combination of indices for spinal deformation (SDI, HR, DOW) using a cluster analysis. Back pain was a major complaint in both groups, without differences in pain intensity and frequency. Impairment of general well being and mood was found in about one‐third of the patients in both groups. Independent of age, the disability score was significantly higher in patients with osteoporosis than in patients with CLBP. Both groups differed with respect to clinical measures of spinal deformity (HR, DOW, DIR). Among osteoporotic patients, parameters of quality of life were not linearly related to the degree of radiologically assessed vertebral deformity, but osteoporotic patients with two or more vertebral fractures tended to have more functional limitations than those with only one fracture. There was, however, a significant linear relationship between components of quality of life (disability score, pain) and clinical measures of spinal deformation (HR, DOW, DIR). The osteoporotic patients were subdivided into three clusters. The first group was characterized by low spinal deformation (↓SDI, ↓HR, ↓DOW) and little impairment of quality of life. The second group had significantly greater spinal deformation (↑SDI, ↑HR, ↑DOW) and significantly more pain and functional limitations. The third group was characterized by increased kyphosis, mainly caused by nonskeletal dysfunction (↓SDI, ↓HR, ↑DOW), but pain and functional limitations were impaired to the same degree as in the second group with severe skeletal spinal deformation. We conclude that with respect to quality of life components, functional limitation is the most specific to spinal osteoporosis and is related to clinical measures of spinal deformation. Furthermore, spinal deformation and the clinical course of osteoporosis appears to be insufficiently reflected by radiological indices of vertebral deformity (such as SDI) alone. For grading the disease and for therapeutical concepts, radiological measures and clinical evaluation should be considered in combination.

Effects of a new spinal orthosis on posture, trunk strength, and quality of life in women with postmenopausal osteoporosis: a randomized trial.

Pfeifer M, Begerow B, Minne HW: Effects of a new spinal orthosis on posture, trunk strength, and quality of life in women with postmenopausal osteoporosis: A randomized trial. Am J Phys Med Rehabil 2004;83:177–186. ObjectiveOne fourth of women ≥50 yrs of age in the general population have one or more vertebral fractures. The orthotic treatment modality in the management of vertebral fractures caused by osteoporosis remains subjective because no objective data from clinical trials are available. The objective of this research was to evaluate the efficacy of a newly developed spinal orthosis in patients with osteoporotic vertebral fractures. DesignWe conducted a study that measured trunk muscle strength, angle of kyphosis, body height, body sway, and variables of quality of life such as pain, well-being, and limitations of daily living. ResultsWearing the orthosis for 6-mo period was associated with a 73% increase in back extensor strength, a 58% increase in abdominal flexor strength, an 11% decrease in angle of kyphosis, a 25% decrease in body sway, a 7% increase in vital capacity, a 38% decrease in average pain, a 15% increase in well-being, and a 27% decrease in limitations of daily living. The overall tolerability of the orthosis was good, no side-effects were reported, and the drop-out rate of 3% was rather low. ConclusionsThe use of an orthosis increases trunk muscle strength and thus improves posture in patients with vertebral fractures caused by osteoporosis. In addition, a better quality of life is achieved by pain reduction, decreased limitations of daily living, and improved well-being. Therefore, the use of an orthosis may represent an efficacious nonpharmacologic treatment option for spinal osteoporosis.

Quality of life as outcome in the treatment of osteoporosis : The development of a questionnaire for quality of life by the European Foundation for Osteoporosis

The morbidity of osteoporosis is caused by fractures. Vertebral fractures lead to pain and disability and a decrease in quality of life. A Working Party of the European Foundation for Osteoporosis has developed a specific questionnaire for patients with established vertebral osteoporosis. This questionnaire is intended for use in clinical trials. The questionnaire consists of questions and visual analogue scales in the following domains: pain, activities of daily living, jobs around the house, mobility, leisure and social activities, general health perception and mood. The questionnaire has been translated from English into French, German, Italian, Hebrew, Swedish and Dutch. The questionnaire is currently being validated in a multicentre study involving patients with stable osteoporosis and control subjects. Preliminary results indicate that the reproducibility is sufficient and that the questionnaire is able to discriminate between patients with vertebral osteoporosis and control subjects.

Musculoskeletal Rehabilitation in Osteoporosis: A Review†

Measures of musculoskeletal rehabilitation play an integral part in the management of patients with increased fracture risk because of osteoporosis or extraskeletal risk factors. This article delineates current scientific evidence concerning nonpharmacologic approaches that are used in conjunction with pharmacotherapy for prevention and management of osteoporosis.

Paget's Disease of Bone: Histologic Analysis of 754 Patients

Although Pagets disease of bone (PDB) is the second most common metabolic bone disease, to our knowledge, there is only one quantitative analysis on the histological and especially on the histomorphometric level. Therefore, the aim of this study was to analyze, on the basis of the Hamburg Bone Register, PBD in terms of incidence, skeletal distribution, malignant transformation, and histological and histomorphometric characteristics. Bone biopsies and patient files of 754 cases with histologically proven PDB were reviewed in a retrospective study. Quantitative static histomorphometry was performed on a representative subgroup of 247 biopsies derived from patients with manifestation of PDB at the iliac crest and compared with an age‐ and sex‐matched control group. The peak incidence of PDB was between 70 and 80 yr of age. The majority of monostotic skeletal manifestation was localized at the os ilium, followed by the spine and femur. Histomorphometric results showed a high bone turnover with a significant increase in bone resorption and bone formation indices leading to an increased bone volume. Paget sarcoma was diagnosed in 6 of 754 patients, indicating a malignant transformation in 0.8% of the affected patients. Taken together, our study characterizes PDB in Germany on the basis of one of the largest cohorts of patients with histologically proven PDB. Moreover, for the first time, a quantitative histomorphometric approach was taken for >200 cases, where we could show local high bone mass lesions as a result of an increase of both osteoclast and osteoblast indices.