Effects of two newly developed spinal orthoses on trunk muscle strength, posture, and quality-of-life in women with postmenopausal osteoporosis: a randomized trial.

OBJECTIVES: We conducted a prospective randomized study to evaluate the efficacy of two newly developed spinal orthoses in patients with vertebral fractures. DESIGN: We conducted a prospective, randomized, cross-over study to evaluate the efficacy of two newly developed spinal orthoses in patients with osteoporotic vertebral fractures. Measurements include trunk muscle strength, angle of kyphosis, body height, body sway, and parameters of quality-of-life such as pain, well-being, and limitations of daily living. RESULTS: Wearing the orthosis Spinomed during a 6-mo period (results of Spinomed active are given in parentheses) was associated with a 72% (64%) increase in back extensor strength (P < 0.01), a 44% (56%) increase in abdominal flexor strength (P < 0.01), an 11% (11%) decrease in the angle of kyphosis (P < 0.01), a 23% (20%) decrease in body sway (P = 0.03 and P = 0.02), a 19% (18%) increase in vital capacity (P < 0.01 and P = 0.03), a 41% (47%) decrease in average pain (P < 0.01), an 18% (18%) increase in well-being (P < 0.01), and a 49% (54%) decrease in limitations of daily living (P < 0.01), respectively. The overall tolerability of the orthoses was good; no adverse effects were reported and the dropout rate with 7% was rather low. CONCLUSIONS: The use of an orthosis increases trunk muscle strength and therefore 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. Thereby, the use of an orthosis may represent an efficacious nonpharmacologic treatment option for spinal osteoporosis.

The role of exercise in the treatment of osteoporosis.

The objective of exercise in the treatment of osteoporosis is to improve axial stability through improvement of muscle strength. Therefore, a back extension exercise program specific to one's musculoskeletal competence and pain can be performed in a sitting position and later advanced to the prone position. When fragility is resolved, back extension is performed against resistance applied to the upper back. To decrease pain and immobility in acute vertebral fracture, use of spinal orthoses become inevitable. Therapeutic exercise should address osteoporosis-related deformities of axial posture, which can increase risk of fall and fracture. Strengthening of the major appendicular muscles decreases fragility. The effect of strengthening exercise is augmented by proper intake of cholecalciferol and calcium. Thus, the role of a therapeutic exercise program is to increase muscle strength safely, decrease immobility-related complications, and prevent fall and fracture. As with pharmacotherapy, therapeutic exercises are individualized.

Teriparatide following bisphosphonates: initial and long-term effects on microarchitecture and bone remodeling at the human iliac crest.

Since the approval of teriparatide for clinical application, a number of iliac crest studies have focused on increases in bone volume or changes in structural parameters with microCT and numerical changes in histomorphometry. This investigation is based on individual histopathological observations related to early and late effects of teriparatide treatment in humans. A total of 44 (18 paired) iliac crest biopsies (ICB) from 41 patients receiving teriparatide (10 months +/- 6 months) following bisphosphonate (BP) treatment were investigated for hematopoietic changes, bone turnover, and description of microarchitectural changes using histology and selective microCT. Fully 71% of the ICB showed a normal or high bone turnover; 56% of the paired ICB presented an increase in bone turnover following teriparatide treatment. Early teriparatide stimulation (<1 month) resulted in peritrabecular fibroblast-like formations. Rare findings (<9%) included reactive hematopoietic changes, osteoidosis, endosteal fibrosis, microcallus, or woven bone. Round mast cells were frequently observed within marrow spaces. A total of 14% had an increase in cortical porosity, approximately 20% demonstrated signs of intratrabecular resorption sites. Teriparatide treatment resulted in an increase in remodeling units as early as 1 week after the first application with a continuous stimulation up to 18 months of rhPTH treatment despite previous BPs. Subgroups of patients developed increased cortical and/or intratrabecular resorption pattern, with unclear biomechanical significance. This mechanism could potentially result in new trabecular structures with an increase in trabecular number. Some individuals presented histological findings (e.g., fibrosis) that may require adjustment of treatment that could be of importance for clinical efficacy.

Alendronate/vitamin D3 70 mg/2800 IU with and without additional 2800 IU vitamin D3 for osteoporosis: results from the 24-week extension of a 15-week randomized, controlled trial.

Although vitamin D supplementation is a fundamental part of osteoporosis treatment, many patients do not regularly take adequate amounts. A once-weekly (OW) alendronate (ALN) preparation that includes 2800 IU of vitamin D3 in a single combination tablet (ALN+D2800) is available for treating patients and ensuring intake of vitamin D that is consistent with existing guidelines. This randomized, double-blind study extension was conducted to evaluate the safety and tolerability of ALN+D2800 and ALN+D2800 plus an additional 2800 IU vitamin D3 single tablet supplement (ALN+D5600) administered for 24 weeks in men and postmenopausal women with osteoporosis previously treated OW for 15 weeks with either ALN or ALN+D2800. The primary endpoint was the proportion of participants who developed hypercalciuria (defined as a 24-hour urine calcium >300 mg in women or >350 mg in men and an increase of >25% versus randomization baseline) at week 39. The key secondary endpoint was the proportion of participants with vitamin D insufficiency (serum 25(OH)D <15 ng/mL [37.4 nmol/L]) at the end of the study. Hypercalciuria incidence (4.2% [ALN+D5600] vs. 2.8% [ALN+D2800]), did not differ between groups (p = 0.354). No participants developed hypercalcemia. Among the participants with vitamin D insufficiency at the week 0 baseline, the prevalence of insufficiency at the end of the study was reduced by 92% in the ALN+D5600 group and by 86% in the ALN+D2800 group. The incidences of clinical adverse experiences, including drug-related adverse experiences, were similar in both groups. In subjects previously treated with ALN+D2800 for 15 weeks, the addition of 2800 IU D3 for 24 weeks did not produce hypercalcemia nor increase the risk of hypercalciuria.

Paget's disease of bone: histologic analysis of 754 patients.

Although Paget's 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.

Bone density after teriparatide in patients with or without prior antiresorptive treatment: one-year results from the EUROFORS study.

OBJECTIVE: Recombinant teriparatide, a bone anabolic agent, is given to treatment-naïve and pre-treated patients with severe osteoporosis, but few data exist comparing the response to teriparatide in these groups. EUROFORS (the EUROpean study of FORSteo‡) enrolled postmenopausal women with established osteoporosis who were either treatment-naïve or had prior antiresorptive (AR) treatment with or without documented inadequate clinical response. The objective of the secondary analysis described here was to evaluate the interim bone mineral density (BMD) response in these groups after one year of open-label teriparatide therapy. RESEARCH DESIGN AND METHODS: Postmenopausal women with established osteoporosis who enrolled in a prospective, randomized, controlled trial received open-label teriparatide 20 µg/day for the first year. With respect to their prior osteoporosis treatment history, they were retrospectively allocated to one of three groups: treatment-naïve (n = 204), prior treatment with an antiresorptive drug (AR-pretreated) (n = 240), or prior antiresorptive treatment with inadequate response (inadequate AR-responders) (n = 421). BMD was measured by dual energy x-ray absorptiometry. RESULTS: Lumbar spine BMD increased from baseline (p < 0.001) in the three groups (mean, 95% CI); treatment-naïve: 8.4% (7.4%, 9.3%); AR-pretreated: 7.1% (6.3%, 7.9%); inadequate AR-responders: 6.2% (5.6%, 6.9%). Total hip BMD increased from baseline in the treatment-naïve (p < 0.001): 1.8% (1.1%, 2.5%) but did not change in the AR-pretreated: 0.4% (-0.2%, 1.1%) or inadequate AR-responders: -0.3% (-0.9%, 0.2%). Treatment-emergent adverse events were similar in the three groups. CONCLUSION: One year of teriparatide significantly (p < 0.001) increased spine BMD in all groups, and total hip BMD in the treatment-naïve group. Because of the limitations of this interim analysis (most importantly, the short duration of treatment and lack of a control group), further study is needed to determine the optimal treatment duration to reach the potential BMD gains at the proximal femur in patients with prior antiresorptive drug use (mostly bisphosphonates). CLINICAL TRIAL REGISTRATION: clinicaltrials.gov, nct00191425.

Treatment preference for monthly oral ibandronate and weekly oral alendronate in women with postmenopausal osteoporosis: A randomized, crossover study (BALTO II).

OBJECTIVES: Patient preference strongly influences long-term medication use in chronic diseases such as postmenopausal osteoporosis. METHODS: This 6-month, open-label, crossover, international study randomized 350 women with postmenopausal osteoporosis to monthly oral ibandronate 150mg for 3months followed by weekly alendronate 70mg for 12weeks, or vice versa. RESULTS: Of patients expressing a preference (93.1%), more preferred the monthly ibandronate regimen (70.6%) than the weekly alendronate regimen (29.4%). The monthly ibandronate preference rate was statistically significant (P<0.0001). The most common reasons for ibandronate preference were ease of staying on treatment long-term (81.5%) and better lifestyle fit (75.4%). More women found the monthly ibandronate regimen more convenient (76.6%) than the weekly alendronate regimen (23.4%). The monthly ibandronate convenience rate was statistically significant (P<0.0001). The safety profiles of the two regimens were similar. CONCLUSION: The strong patient preference for monthly ibandronate over weekly alendronate replicates previous study findings and may lead to improved treatment adherence in women with postmenopausal osteoporosis.

[Use of imaging procedures in the diagnostics of osteoporosis interpretation of x-rays and bone density measurements]. / Einsatz bildgebender Verfahren bei der Diagnostik der Osteoporose Interpretation der Röntgenbilder und Messprotokolle der Knochendichte.

According to the recently published BoneEVA study, 7.8 million Germans (6.5 million women) are affected by osteoporosis. Of them, 4.3% experienced at least one clinical fracture. Only 21.7% were treated with an anti-osteoporotic drug, whereby only 10% received a bisphosphonate and 17% given calcium and vitamin D. On the other hand, as osteoporosis may be associated with severe pain in 90% of patients, analgesics are prescribed. The total direct costs attributable to osteoporosis amounted to Euro 5.4 billion in 2003. One out of three postmenopausal women and one out of five men over the age of 50 years will experience osteoporotic fractures unless preventive measures are undertaken. According to the German guidelines for diagnosis and treatment of osteoporosis, bone densitometry using dual energy x-ray absorptiometry (DXA) together with other clinical risk factors (previous low trauma fracture, use of nicotine, low body weight [BMI<20 kg/m2], immobilisation, and more than two falls during the last six months) are recommended for diagnosis. Using typical cases out of clinical practice, this article delineates frequent mistakes in the interpretation of DXA measurements. Furthermore, the present paper clarifies the role of classical x-rays, which still represent the predominant procedure for the identification of fractures and especially vertebral fractures. In comparison to x-rays, CT or MRI are more important in differential diagnosis of malignant disease and bone metastases. Essentially a reduction of vertebral height without evidence of central endplate fracture in postmenopausal women may be unrelated to osteoporosis. Quantitative morphometry should not be used alone for the assessment of vertebral fracture in clinical decision-making. Therefore, we recommend differential diagnosis of morphometric vertebral deformities by an expert reader to rule out deformities related to degenerative disease and norm variants of which we will present several examples to train the view of the reader.

[The role of vitamin D in the treatment of osteoporosis in the elderly]. / Zur Bedeutung von Vitamin D in der Osteoporosetherapie.

During the last 5 years several randomized, prospective, placebo-controlled clinical trials have documented that a supplementation with vitamin D (400-1,200 IU per day) together with calcium (800-1,500 mg per day) may reduce the risk of falls and fall-related fractures in the elderly. This is especially the case in elderly women >or= 65 years of age with a serum 25-hydroxy-vitamin-D(3) level < 50 nmol/l. Based on the results of a recently published meta-analysis involving more than 10,000 participants, the grade of evidence according to the Oxford Centre of Evidence-based Medicine is Ia with respect to the primary prevention of falls in the elderly population.

Prospective identification of postmenopausal osteoporotic women at high vertebral fracture risk by radiography, bone densitometry, quantitative ultrasound, and laboratory findings: results from the PIOS study.

Women with established osteoporosis are at high risk to sustain additional vertebral fractures. Treatment may affect the predictive power of bone densitometry and biochemical techniques. There are few prospective studies comparing fracture prediction by dual-energy X-ray absorptiometry (DXA) and other techniques in treated women with established osteoporosis. The objective of this study was to prospectively assess the predictive power of various DXA and quantitative ultrasound (QUS) techniques for identification of women at high risk to develop new fractures over 1-2 yr. Moreover, we wanted to investigate whether previous or ongoing therapy precluded the use of common clinical laboratory blood tests and bone turnover markers for prediction of fracture risk. We measured prevalent fracture status; bone mineral density (BMD) of the whole body, spine, and hip by DXA; QUS of the calcaneus and the patella; hormones and various markers of bone resorption and formation; and took standard blood tests in 124 women (age 64.9 yr +/- 7.9) with manifest and variously treated postmenopausal osteoporosis. Subsequently, new spine fractures were assessed after 1 yr and, in a subset of 87 women, after 2 yr. Prevalent fractures turned out to be the strongest predictor of subsequent vertebral fractures with an age-adjusted odds ratio (OR) of 3.9 per prevalent fracture over 2 yr. Furthermore, our results underline the predictive power of spinal BMD (sOR = 2.1; standardized OR per 1 standard deviation population variance decrease), whole body BMD (sOR: 2.4), and QUS stiffness index of the calcaneus (sOR: 2.8) for vertebral fracture prediction. QUS of the patella did not predict vertebral fractures. Blood sedimentation rate was predictive in the first year (sOR: 1.9). The predictive power of bone turnover markers, however, appeared to be too low to be detectable in a group of this sample size and it may have been reduced because most women were already receiving treatment. In conclusion, radiographic measures, but not the tested laboratory bone turnover markers, enabled us to identify women (from a population of osteoporotic women who have been treated for some time with a variety of medications) who are at highest risk for developing new vertebral fractures within 1-2 yr.

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. Fractures caused by osteoporotic fragility may be prevented with multidisciplinary intervention programs, including education, environmental modifications, aids, and implementation of individually tailored exercise programs, which are proved to reduce falls and fall-related injuries. In addition, strengthening of the paraspinal muscles may not only maintain BMD but also reduce the risk of vertebral fractures. Given the strong interaction between osteoporosis and falls, selection of patients for prevention of fracture should be based on bone-related factors and on risk factors for falls. Rehabilitation after vertebral fracture includes proprioceptive dynamic posture training, which decreases kyphotic posturing through recruitment of back extensors and thus reduces pain, improves mobility, and leads to a better quality of life. A newly developed orthosis increases back extensor strength and decreases body sway as a risk factor for falls and fall-related fractures. Hip fractures may be prevented by hip protectors, and exercise programs can improve strength and mobility in patients with hip fracture. So far, there is no conclusive evidence that coordinated multidisciplinary inpatient rehabilitation is more effective than conventional hospital care with no rehabilitation professionals involved for older patients with hip fracture. Further studies are needed to evaluate the effect of combined bone- and fall-directed strategies in patients with osteoporosis and an increased propensity to falls.

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

OBJECTIVE: One fourth of women > or =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. DESIGN: We 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. RESULTS: Wearing 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. CONCLUSIONS: The 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.