[Pregnancy and lactation-associated osteoporosis]. / Schwangerschaftsassoziierte Osteoporose.

Pregnancy and lactation-associated osteoporosis (PLO) is a rare form of osteoporosis, which occurs in the last trimester or postpartum. So far 100 cases have been published. The leading symptoms are severe low back pain or less frequently hip pain. Many patients develop postpartum depression due to inability to care for the baby and vertebral fractures. The therapeutic decision has to be made individually but teriparatid and bisphosphonates seem to be the best option. We report the clinical course (16 years) of a 37-year-old patient with PLO, who suffered 6 vertebral fractures. There were severe physical limitations and mental problems caused by the disease. The patient was treated by multimodal therapy including physiotherapy and psychotherapy and bisphosphonates were given. The time between the onset of symptoms and diagnosis was 5 months. No further fractures occurred in the following 16 years. The physical and mental condition significantly improved.

[Evaluation and socio-economic relevance of an integrated osteoporosis health care network]. / Evaluation und sozio-ökonomische Bewertung eines Modells zur Integrierten Versorgung zur Behandlung der Osteoporose.

During the last 6 to 7 years, integrated health care has become more and more important in Germany. In August 2005 we initiated a collaborative project involving two orthopaedic clinics in Hanover and one rehabilitation clinic in Bad Pyrmont specialising in the treatment of osteoporosis. Here, we report the results of 633 women (83 ± 7 years) and 162 men (75 ± 10 years) who participated in this programme between August 2005 and August 2012. All participants gave informed consent. All patients were supplemented with 1200 mg of calcium and 800 IU of vitamin D. Intravenous bisphosphonates were given to 91% and parathyroid hormone to 7% of the patients. Two per cent received miscellanous therapeutic agents. Follow-up visits were attended by 89% of the patients after one year and 78% after two years. During this time, a significant improvement was observed in vitamin D, parathyroid hormone and the bone marker desoxypyridinoline. DXA measurements were falsified by degenerative disease or fractures. In the men, however, a significant increase was observed in the total hip. Over the two-year period, 16 vertebral and 3 non-vertebral fractures occurred in the women. In the men, one non-vertebral and 5 vertebral fractures were noted. Among the women, 18 died and 6 were admitted to a nursing home. The corresponding figures among the men were 7 and 4, respectively. According to the figures provided by the central German institute for statistics, the death rates among the women were significantly lower than expected, whereas a tendency toward lower death rates was seen in the men. In addition, the number of new hip fractures in the women was lower than the epidemiological data suggest. This was also noted in the men. Even among the very old, a musculoskeletal rehabilitation programme combined with adequate pharmaceutical therapy may prove very successful when it comes to death rates and nursing home admissions. The latter in particular may be very expensive in the long run and our longitudinal follow-up study may demonstrate cost-effectiveness if the rehabilitation programme is commenced as early as possible.

Increased osteoblast and osteoclast indices in individuals with systemic mastocytosis.

UNLABELLED: Indolent systemic mastocytosis (ISM) can trigger bone loss. However, the clinical relevance of different mast cell infiltration patterns for bone remains to be clarified. Here, we report increased bone turnover in individuals with ISM, and its extent is rather related to the type of mast cell distribution within the bone marrow than to the presence or absence of cutaneous manifestations. INTRODUCTION: It is well established that ISM can trigger osteopenia or osteoporosis. However, neither the clinical relevance of the infiltration pattern of mast cells within the bone marrow nor the impact of the presence or absence of cutaneous mast cell infiltration has been elucidated. METHODS: We retrospectively analysed 300 cases with histologically proven ISM of the bone marrow and performed quantitative histomorphometry for a subgroup of 159 patients that did not receive any treatment before the biopsies were taken. Most importantly, since 66 % of the patients displayed ISM without the characteristic skin lesions, we were able to compare ISM with or without cutaneous manifestation. RESULTS: We found that both forms of ISM were not only characterized by a decreased trabecular bone mass but also by an increased number of osteoclasts and osteoblasts. Interestingly, when we analysed these data in relation to mast cell distribution, we found that the bone cell numbers in cases with mast cell granulomas were significantly increased compared to cases with diffuse mast cell distribution. Moreover, evidence of increased bone turnover was also found in 16 patients displaying osteosclerosis. CONCLUSION: Based on the largest cohort of bone biopsies from patients with ISM analysed so far, we could demonstrate high bone turnover, more specifically increased osteoblast and osteoclast numbers and surface indices, as a cause of the skeletal changes. Moreover, the severity of the bone disease is presumably rather dependent on the amount of mast cells and their distribution within the bone marrow irrespective of the presence or absence of cutaneous involvement.

[Medical training therapy with special consideration to osteoporosis of the spinal column]. / Medizinische Trainingstherapie unter besonderer Berücksichtigung der osteoporotischen Wirbelsäule.

Medical training therapy (MTT) plays a decisive role in maintenance and development of musculoskeletal health of humans in all phases of life. In childhood and adolescence it can contribute to the highest possible so-called peak bone mass and thus avoid or delay the appearance of osteoporosis for as long as possible, in view of increased life expectations. In young adults targeted MTT is well suited to improve performance and to maintain the maximum developed bone mass. The latter is also true for perimenopausal and postmenopausal women in whom MTT can compensate for the loss of bone mass due to hormone deficiency in comparison to those not in training. Elderly people who have possibly already suffered several fractures and who are in danger of becoming permanently dependent on external help due to increasing fragility can still improve muscle strength and mass by regular MTT even in advanced age. This will reduce or avoid the risk of falling and maintain the ability to be self-sufficient for as long as possible. In order to support this, rehabilitation measures even in-hospital, could be useful and should be especially promoted in line with the amendments to the social legislation effective from 1st April 2007 ("Rehabilitation before nursing").

Effect of glucocorticoid-, parathyroid- and thyroid hormones excess on human iliac crest bone matrix insulin-like growth factor (IGF)-I in patients with osteoporosis.

Insulin-like growth factor-I (IGF-I) is a well documented bone-active growth factor. Clinical studies reported that circulating hormones may affect serum IGF-I levels, with potential consequences on bone remodeling. However, no data on bone matrix concentrations of IGF-I in subjects with endocrine dysfunction is available in humans. Bone mineral density and cancellous bone matrix IGF-I levels were assessed in iliac crest biopsies from 38 patients with low bone mass related to glucocorticoid- (n=10), parathyroid- (n=14) or thyroid (n=14) hormones excess. Results were compared to those of sex- and age-matched patients with primary osteoporosis. Bone matrix extraction was performed based on a guanidine-chlorhidric acid/ethylendiamine-tetraacetic acid method. Long-term glucocorticoid therapy (> or =24 months) led to significantly lower cancellous bone matrix IGF-I levels in comparison to age-matched controls (p=0.03). Although higher trabecular bone IGF-I levels were seen in hyperparathyroid subjects, the difference was not significant in comparison to controls (p=0.24). Likewise, no difference was noticed in cancellous bone matrix IGF-I concentrations between subjects with low bone mass and sub-clinical or overt thyrotoxicosis and euthyroid controls. Neither parathyroid hormone (PTH) nor thyroxin (T (4)) concentrations were associated with bone matrix IGF-I levels. To conclude, our study documented that in vivo long-term corticotherapy is associated with low trabecular human bone matrix IGF-I. In contrast, no influence of increased circulating parathyroid- or thyroid hormones levels on human iliac crest skeletal IGF-I concentrations was observed.

Effects of a long-term vitamin D and calcium supplementation on falls and parameters of muscle function in community-dwelling older individuals.

UNLABELLED: In 242 community-dwelling seniors, supplementation with either 1000 mg of calcium or 1000 mg of calcium plus vitamin D resulted in a decrease in the number of subjects with first falls of 27% at month 12 and 39% at month 20. Additionally, parameters of muscle function improved significantly. INTRODUCTION: The efficacy of vitamin D and calcium supplementation on risk of falling in the elderly is discussed controversially. Randomized controlled trials using falls as primary outcome are needed. We investigated long-term effects of calcium and vitamin D on falls and parameters of muscle function in community-dwelling elderly women and men. METHODS: Our study population consisted of 242 individuals recruited by advertisements and mailing lists (mean [ +/- SD] age, 77 +/- 4 years). All serum 25-hydroxyvitamin D (25[OH]D) levels were below 78 nmol/l. Individuals received in a double blinded fashion either 1000 mg of calcium or 1000 mg of calcium plus 800 IU of vitamin D per day over a treatment period of 12 months, which was followed by a treatment-free but still blinded observation period of 8 months. Falls were documented using diaries. The study took place in Bad Pyrmont, Germany (latitude 52 degrees ) and Graz, Austria (latitude 46 degrees ). RESULTS: Compared to calcium mono, supplementation with calcium plus vitamin D resulted in a significant decrease in the number of subjects with first falls of 27% at month 12 (RR = 0.73; CI = 0.54-0.96) and 39% at month 20 (RR = 0.61; CI = 0.34-0.76). Concerning secondary endpoints, we observed significant improvements in quadriceps strength of 8%, a decrease in body sway of 28%, and a decrease in time needed to perform the TUG test of 11%. DISCUSSION: Combined calcium and vitamin D supplementation proved superior to calcium alone in reducing the number of falls and improving muscle function in community-dwelling older individuals.

Post-fracture management of patients with hip fracture: a perspective.

BACKGROUND: Hip fracture creates a worldwide morbidity, mortality and economic burden. After surgery, many patients experience long-term disability or die as a consequence of the fracture. A fracture is a major risk factor for a subsequent fracture, which may occur within a short interval. METHODS: A literature search on post-fracture management of patients with hip fracture was performed on the Medline database. Key experts convened to develop a consensus document. FINDINGS: Management of hip-fracture patients to optimize outcome after hospital discharge requires several stages of care co-ordinated by a multidisciplinary team from before admission through to discharge. Further studies that specifically assess prevention and post-fracture management of hip fracture are needed, as only one study to date has assessed an osteoporosis medication in patients with a recent hip fracture. Proper nutrition is vital to assist bone repair and prevent further falls, particularly in malnourished patients. Vitamin D, calcium and protein supplementation is associated with an increase in hip BMD and reduction in falls. Rehabilitation is essential to improve functional disabilities and survival rates. Fall prevention and functional recovery strategies should include patient education and training to improve balance and increase muscle strength and mobility. Appropriate management can prevent further fractures and it is critical that high-risk patients are identified and treated. To foster this process, clinical pathways have been established to support orthopaedic surgeons. CONCLUSION: Although hip fracture is generally associated with poor outcomes, appropriate management can ensure optimal recovery and survival, and should be prioritized after a hip fracture to avoid deterioration of health and prevent subsequent fracture.

Concentration of insulin-like growth factor (IGF)-I in iliac crest bone matrix in premenopausal women with idiopathic osteoporosis.

Previous studies have shown a link between low serum insulin-like growth factor-I (IGF-I) and decreased bone mass of patients with osteoporosis. However, whether serum levels are representative for the growth factor concentration or activity available in human bone tissue is controversial. In the present study, IGF-I was assessed in serum and bone matrix extracts from the iliac crest in 19 eugonadal women with idiopathic osteoporosis and in 38 age-matched controls. In addition, the relationship between the skeletal levels of IGF-I and bone mineral density (BMD) or the susceptibility to osteoporotic fractures in women with osteoporosis was examined. Bone matrix extraction was performed based on a guanidine-HCL/ethylendiamine-tetraacetic acid (EDTA) method. No significant difference in both serum and bone matrix IGF-I levels between groups was observed. Serum IGF-I concentrations failed to be associated with bone matrix IGF-I levels in osteoporotic patients. However, in premenopausal women with idiopathic osteoporosis, skeletal IGF-I positively correlated with BMD at the lumbar spine (r = + 0.58, p = 0.01). In contrast, neither femoral neck BMD nor Ward's triangle BMD was associated with bone matrix IGF-I concentrations. A tendency towards lower levels of bone matrix IGF-I in subjects with vertebral fractures as compared to those without fractures was observed in age-adjusted analyses, however the difference failed to remain statistically significant after adjustment for bone mineral density. These data provide no clear evidence for low bone matrix IGF-I as a determinant factor of age-unrelated osteoporosis. However, low skeletal IGF-I concentrations may aggravate osteoporosis in these women.

Influence of fluor salts, hormone replacement therapy and calcitonin on the concentration of insulin-like growth factor (IGF)-I, IGF-II and transforming growth factor-beta 1 in human iliac crest bone matrix from patients with primary osteoporosis.

OBJECTIVE: Data from cell culture experiments suggest that local growth factors (GFs) may mediate the effects of estrogens, calcitonin or fluor ions on the skeleton. To assess the in vivo relevance of the in vitro reports, the effect of fluor salts, hormone replacement therapy (HRT) and calcitonin on the concentrations of IGF-I, IGF-II and transforming growth factor (TGF)-beta 1 in bone matrix extracts from osteoporotic patients was evaluated. DESIGN: Iliac crest bone biopsies were obtained from 170 patients (76 men and 94 women) with primary osteoporosis aged 55.5+/-0.8 Years. METHODS: Bone matrix extraction was performed based on a guanidine-HCl/ethylendiamine-tetra-acetic acid method. RESULTS: In comparison with age- and body mass index (BMI)-matched controls, no influence of long-term therapy with fluor ions (n=41) or calcitonin (n=16) on the bone matrix concentration of GFs was noticed. Postmenopausal women with osteoporosis on HRT (n=39) had lower skeletal IGF-I but not IGF-II levels as compared with age- and BMI-matched non-users. However, the lower rate of bone turnover in women with HRT may account for this difference, since the significance was lost after adjustment for alkaline phosphatase. Likewise, a tendency for lower TGF-beta 1 levels was observed in HRT users as compared with non-users but was lost after adjustment for bone turnover. None of the therapies influenced the serum levels of GFs when patients receiving continuous therapy for at least 1 Year before bone biopsy were considered. CONCLUSIONS: Our data suggest no direct effect of fluor therapy on skeletal GFs levels. At the concentrations used, neither HRT nor calcitonin appeared to exert any significant influence on serum or bone matrix GF levels.

Bone matrix insulin-like growth factor (IGF)-I, IGF-II and transforming growth factor (TGF)-beta1 levels in men and postmenopausal women with osteoporosis: lack of association with circulating growth factors and bone mineral density.

Previous clinical studies have suggested a positive correlation between serum insulin-like growth factor components and bone mass in both men and women with or without osteoporosis. The aim of the present study was to analyze the relationship between the skeletal levels of insulin-like growth factors and transforming growth factor-b1 and bone mineral density in a group of men and postmenopausal women in whom osteoporosis was diagnosed previously. Bone matrix extraction was achieved by passive dialysis against tetrasodium EDTA-guanidine-HCL. IGF's were quantified by radioimmunoassay. TGF-b1 was assessed by a specific enzyme-linked immunoassay. No correlation between BMD and the concentration of IGF-I, IGF-II and TGF-b1 in bone matrix was detected in either men or postmenopausal women with osteoporosis. In addition, circulating growth factors levels failed to be associated with the concentration of IGF-I, IGF-II and TGF-b1 in the skeleton. Thus, our study provides no evidence for a major role of bone matrix IGF's or TGF-b1 as determinants of bone mass in men or postmenopausal women with osteoporosis.

[Weeks of pain, vertebral body fractures during sleep, invalidism. Save your osteoporosis patients from this fate]. / Wochenlange Schmerzen, Wirbelbruch im Schlaf, Invalidität. Ersparen Sie Ihren Osteoporose--patienten diese Folgen!

In terms of their clinical impact, bone fractures as late sequelae of osteoporosis are still largely ignored in Germany. Up to 80-90% of patients with treatment-requiring osteoporosis are not receiving specific treatment. The consequences for the patient are enormous: weeks of severe pain, subsequent fractures that occur for ever more banal reasons, increasing restriction of daily activities, invalidism and an increasing need for nursing care. All this despite the availability of powerful medications. In concert with an appropriate early diagnosis, not only could the majority of patients be spared such a fate, but also the costs incurred as a direct consequence of such fractures could be drastically lowered.

Transdermal fentanyl for the treatment of back pain caused by vertebral osteoporosis.

Pain relief for patients with osteoporosis is important to maintain mobility and facilitate physical therapy. Transdermal fentanyl may be useful but has not been studied systematically. Patients with at least one osteoporotic vertebral fracture requiring strong opioids were enrolled and received transdermal fentanyl. Treatment history, pain, ease of physical therapy, and quality of life were recorded at baseline and after 4 weeks. Of 64 patients enrolled, 49 completed the study; 12 withdrew because of adverse events, most commonly nausea, vomiting, or dizziness. Pain at rest and on movement decreased significantly from baseline to final assessment (mean scores 7.84 and 8.55, respectively, at baseline, falling to 3.56 and 4.50 after 4 weeks). Quality of life improved significantly, and 61% of patients were satisfied with the treatment. Ability to undergo physical therapy improved significantly. Transdermal fentanyl is useful for the treatment of severe back pain caused by osteoporosis.

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 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.

[Osteoporosis - Evidence based therapy]. / Osteoporose: Umgang mit einer Stoffwechselkrankheit der Knochen unter Berücksichtigung der Prinzipien einer auf Evidenz basierenden Medizin.

Osteoporosis therapy has been controversially discussed in the past. In the meantime, several therapeutic options to prevent fractures are available for this disease. With respect to proven fracture benefit, however, the quality of evidence from randomised and controlled clinical trials varies substantially among therapies. From systematic research the best external evidence is available for a supplementation with calcium and vitamin D and a therapy with the bisphosphonates alendronate or risedronate, as well as the SERM raloxifene. For other therapeutic agents like fluorides, vitamin D metabolites, calcitonin and etidronate the quality of evidence is much lower. So far, there is no evidence for other pharmaceutical therapies. Hip protectors are effective in the prevention of hip fractures.