Myostatin and markers of bone metabolism in dermatomyositis.

BACKGROUND: In dermatomyostis (DM) patients, inflammation, reduced activity, and medication have a negative impact on the musculoskeletal system. Several endocrine factors are involved in muscle growth and bone turnover. OBJECTIVE: We aimed to investigate factors regulating myogenesis and bone metabolism and to evaluate possible associations between these endocrine factors, muscle strength, and functional tests in DM patients. METHODS: We conducted a cross-sectional study in 20 dermatomyositis patients. Serum levels of myostatin (MSTN), follistatin (FSTN), dickkopf 1 (Dkk1), sclerostin (SOST), periostin (PSTN), the receptor activator nuclear factor kB ligand (RANKL):osteoprotegerin (OPG) ratio and fibroblast growth factor 23 (FGF23) were determined. Physical function was evaluated by hand-held strength measurement, chair rising test, timed up and go test and the 3-min walking test. RESULTS: Serum MSTN and FGF23 levels (2.5 [1.9; 3.2] vs. 1.9 [1.6; 2.3] and 2.17 [1.45; 3.26] vs. 1.28 [0.79; 1.96], respectively; p <  0.05) were significantly higher in DM patients than in controls. Dkk1 was significantly lower (11.4 [6.9; 20.0] vs. 31.8 [14.3; 50.6], p <  0.01). Muscle strength and physical function tests correlated with each other (e.g. hip flexion - timed up and go test: r = - 0.748, p < 0.01). CONCLUSION: In DM patients, biochemical musculo-skeletal markers are altered and physical function shows deficits. All these tests reflect independent of each other different deficits in long-term DM patients which is important for the assessment of DM patients as well as planning of therapeutic interventions in clinical routine.

Neoadjuvant Chemotherapy with Gemcitabine plus Cisplatin in Patients with Locally Advanced Bladder Cancer.

BACKGROUND: Neoadjuvant chemotherapy with methotrexate-vinblastine-doxorubicin-cisplatin (MVAC) is the standard of care for muscle-invasive urothelial bladder cancer. Gemcitabine plus cisplatin (GC) shows similar efficacy with less toxicity in the metastatic setting and has therefore often been used interchangeably with MVAC. We report on the efficacy and safety of neoadjuvant GC in patients with locally advanced urothelial cancer. MATERIALS AND METHODS: We prospectively evaluated 87 patients in 2 centers. Their median age was 68 years. Treatment consisted of 3× GC prior to radical cystectomy. The primary endpoint was pathologic response. The secondary endpoints were safety, progression-free survival (PFS), and overall survival (OS). RESULTS: In all, 83 patients finished chemotherapy; 80 patients were evaluable for the primary endpoint. Pathologic complete response (pCR) was achieved in 22.5% and near pCR was seen in 33.7% of the patients. The 1-year PFS rate was 79.5% among those patients achieving ≤pT2 versus 100% among those patients achieving pCR or near pCR (p = 0.041). Five-year OS was 61.8% (95% CI 67.6 to NA). GC was well tolerated. Grade 3/4 toxicities occurred in 38% of the patients. There was no grade 3/4 renal toxicity, febrile neutropenia, or death. CONCLUSION: Neoadjuvant GC is a well-tolerated regimen. Although the pathologic response is lower than that reported with MVAC, our data support GC as a feasible option in the absence of a prospective randomized comparison, particularly for older patients, since its toxicity is lower than that of MVAC.

Serum levels of sclerostin and dickkopf-1: effects of age, gender and fracture status.

BACKGROUND: Fragility fractures, especially hip fractures, are a very common complication of osteoporosis in elderly subjects. Sclerostin (SOST) and dickkopf-1 (DKK-1) are inhibitors of the canonical wnt signalling pathway and thus could be involved in the pathogenesis of age-related bone fragility. OBJECTIVE: To investigate SOST and DKK-1 in a large group of geriatric patients with hip fractures and to relate the wnt inhibitors to age and gender. METHODS: This was a cross-sectional study carried out in a department of acute geriatric care in a district hospital in Upper Austria and a hospital in Vienna, Austria. A total of 256 geriatric patients (172 women and 84 men) and 67 young control subjects were selected after exclusion. Medical history was obtained, a comprehensive geriatric assessment was performed and serum levels of SOST, DKK-1 and bone formation markers were analysed. RESULTS: DKK-1 levels increased with age and in the presence of hip fractures. In contrast, SOST levels were lower in patients with hip fractures. When compared to women, men had higher SOST levels but lower DKK-1 levels. CONCLUSION: Serum levels of the inhibitors of the canonical wnt signalling pathway reflect different biological events and are useful for the study of bone fragility in geriatric patients.

[Osteoporosis in men receiving androgen deprivation therapy for non-metastatic prostate cancer]. / Osteoporose beim Mann mit hormonablativer Therapie bei nicht-metastasiertem Prostatakarzinom.

Osteoporosis is defined as a continuous loss of bone mineral density accompanied by an increased fracture risk in females and males. A fall of estrogen concentrations at the menopause and the consecutive rapid bone loss are an established pathogenic mechanism in female osteoporosis. Males do not have a menopause equivalent during which significant amounts of bone are lost. Several diseases, therapeutic strategies and nutritional deficiencies may also result in bone loss and reduced bone mineral density. Prostate cancer is the most common visceral malignancy in men. Suppression of endogenous androgen production as a therapeutic tool is commonly used in patients with non-metastatic prostate cancer and is associated with significant bone loss and an increased fracture risk. Androgen deprivation therapy is prescribed both for men with locally advanced or high-risk non-metastatic prostate cancer. Osteoclast inhibition with any of several bisphosphonates improves bone mineral density and reduces fracture risk. Denosumab (a monoclonal antibody against RANK ligand) and toremifene (a selective estrogen receptor modulator) recently have been shown to be effective to reduce vertebral fractures in patients with non-metastatic prostate cancer receiving androgen-deprivation therapy. This overview focuses on cancer-treatment-induced bone loss in patients with non-metastatic prostate cancer.

[Case report of a patient with renal cell cancer and his fateful progress - Breaking Bad News]. / Ein Patient mit schicksalhaftem Verlauf nach Nephrektomie bei Hypernephrom Überbringen schlechter Nachrichten ("Braking Bad News").

"Breaking Bad News" outlines a pathway for medical and other professional staff to deliver bad news to patients, clients, their families and carers. Bad news can mean different things to different people. Basically, it means any information which adversely and seriously affects an individual point of view of future or situations without any feeling of hope. The way a doctor or other health or social care professionals deliver bad news places an indelible mark on the doctor/professional-patient relationship. The debate about the levels of truth given to patients about their diagnosis has developed significantly over the last few years. While doctors and professionals now increasingly share information it has been the practice to withhold information because it was believed to be in the best interests of the patient. We discuss the situation of a patient with renal cancer who developed metastases after surgery. Unfortunately a tumour embolism from the kidney flashed into the pulmonary arteries. First it was not for sure if there were any metastases beside the tumour embolus. Months after embolectomy by thoracic surgery there was certain evidence of multiple pulmonary nodal lesions. First and second line chemotherapies failed and the patient died within several months after start of pharmacologic treatment. The case report discusses diagnosis and procedures, how the patient was supported and the way he got information at any critical date.

Update on denosumab in postmenopausal osteoporosis--recent clinical data.

Denosumab, a fully human monoclonal antibody against the key osteoclastogenic factor RANK ligand, is currently approved for the treatment of postmenopausal osteoporosis. Denosumab differs from bisphosphonates in many aspects, for example, its ability to act in the extracellular compartment and its likelihood to be distributed throughout the skeleton. In contrast, bisphosphonates have to be internalized by osteoclasts and are mainly located across bone surfaces. This could explain why patients with osteoporosis, who are already treated with bisphosphonates, might experience further benefit when switching to denosumab. Head-to-head studies revealed that transition to denosumab resulted in a greater increase of bone mineral density (BMD) and a greater reduction of bone turnover than did continued alendronate. Additional analyses of the phase 3 FREEDOM trial demonstrated that fracture reduction was particularly high in cortical bone, such as the wrist. In addition, denosumab treatment for a 5- and 8-year period showed sustained reduction in fracture risk, increase in BMD and continued to be well tolerated. The 7-year extension study of FREEDOM and a phase 3 trial evaluating denosumab for the treatment of male osteoporosis are still ongoing and will provide supportive data in the near future.

Biomarkers of bone turnover in diagnosis and therapy of osteoporosis: a consensus advice from an Austrian working group.

AIM: Reasonable application of laboratory parameters in prevention, diagnosis, treatment and therapy monitoring of osteoporosis. TARGET GROUPS: Physicians from different specialist disciplines (general medicine, geriatrics, gynaecology, urology, internal medicine-especially endocrinology and metabolism, nephrology, laboratory medicine, rheumatology, nuclear medicine, orthopaedics, paediatrics, rehabilitation and physical medicine, radiology, social medicine, transplantation medicine, accident surgery), moreover social insurances, hospitals and self-help groups. BACKGROUND: Evaluation of aetiology of bone disorders, widening of the therapeutic spectrum for diseases of bone and knowledge on biochemical markers of bone turnover. Improvements in judging the success of therapy and in monitoring the compliance of patients. Research perspectives. BASES: Scientific literature and guidelines, consensus meetings. RÉSUMÉ: Basic and specialized laboratory investigations are important in differentiation between primary and secondary osteoporosis for an adequate therapy. Biochemical markers of bone turnover are an additional aid in evaluation of individual fracture risk. These markers identify responders to bone therapy faster than surveillance of bone mineral density, which helps to improve patient's compliance too. Characteristics, preanalytic precautions and applications are presented for selected markers of bone resorption and formation and for parameters regulating bone metabolism.

Circulating bioactive sclerostin levels in an Austrian population-based cohort.

BACKGROUND: Circulating serum sclerostin levels are supposed to give a good estimation of the levels of this negative regulator of bone mass within bone. Most studies evaluating total serum sclerostin found different levels in males compared to females and in older compared to younger subjects. Besides an ELISA detecting total sclerostin an ELISA determining bioactive sclerostin has been developed. The aim of this study was to investigate serum levels of bioactive sclerostin in an Austrian population-based cohort. METHODS: We conducted a cross-sectional observational study in 235 healthy subjects. Using the bioactive ELISA assay (Biomedica) bioactive sclerostin levels were evaluated. RESULTS: Serum levels of bioactive sclerostin were higher in men than in women (24%). The levels correlated positively with age (r = 0.47). A positive correlation could also be detected with body mass index and bone mineral density. CONCLUSION: Using the ELISA detecting bioactive sclerostin our results are consistent with data in the literature obtained by different sclerostin assays. The determination of sclerostin concentrations in peripheral blood thus appears to be a robust parameter of bone metabolism.

Myostatin and other musculoskeletal markers in lung transplant recipients.

Recipients of lung transplantation (LuTx) may experience impaired muscle function and bone metabolism even after rehabilitation. We investigated the potential use of musculoskeletal markers in identifying the impairment of muscle function and bone function in these patients. Biochemical parameters, bodily functions, and lung function of 37 LuTx recipients were evaluated at the time of their discharge from the hospital stay and about 6 months later. The biomarkers were also assessed in 30 healthy age and gender distribution-matched controls. Compared to controls, the negative muscle regulator myostatin was elevated in LuTx recipients at baseline and follow-up, whereas its opponent follistatin only showed a group-specific difference at follow-up. LuTx recipients had reduced serum levels of sclerostin and increased levels of dickkopf 1 and periostin. Lung function and physical function were improved during follow-up. The change in lung function was correlated with the change in chair-rising time and the 6-min walking test. At follow-up, all musculoskeletal markers of LuTx recipients differed from those of controls, thus reflecting their still reduced lung function and bodily functions. Among the tested biomarkers, myostatin, sclerostin, dickkopf 1, and periostin were useful to detect impaired musculoskeletal function in LuTx recipients. Myostatin may serve as a target of treatment in the future.

High cathepsin K levels in men with differentiated thyroid cancer on suppressive L-thyroxine therapy.

BACKGROUND: Thyroid hormone administration is associated with low bone density in some studies. The aim of the present study was to evaluate the influence L-thyroxine, in doses used to treat patients with a history of thyroid carcinoma, on serum cathepsin K and other markers of bone metabolism. Cathepsin K is thought to have a role in osteoclast mediated bone resorption. METHODS: A group of male patients with differentiated thyroid cancer (DTC) on suppressive L-thyroxine therapy (DTC-group; n = 51; mean age 57 years; TSH < 0.1 mU/L) was selected as a model for hyperthyroidism. The results were compared to a group of healthy euthyroid men (control-group; n = 50; mean age 58 years; TSH 1.5 +/- 0.9 mU/L). RESULTS: In the DTC-group the median value of cathepsin K was 6.9 pmol/L, in the control group 4.8 pmol/L (p = 0.0052; highly significant [h.s.]). There was a significant negative correlation of cathepsin K with age (r = -0.279, p = 0.028). The analysis of various bone associated parameters revealed an increase of serum crosslaps in the DTC-group versus euthyroid controls (p = 0.03). A significant correlation could be found for cathepsin K and osteoprotegerin (p = 0.002). CONCLUSION: Cathepsin K is increased by a suppressive L-thyroxine therapy and decreases with increasing age. The increased cathepsin K levels seen in DTC-patients on suppressive L-thyroxine therapy are likely to contribute to accelerated bone degradation in these patients.

Osteoprotegerin plasma concentrations correlate with severity of peripheral artery disease.

OBJECTIVE: Osteoprotegerin (OPG), a member of the tumor necrosis factor receptor family, is involved in the process of bone turnover and also in the pathogenesis of osteoporosis and premature calcification of the vascular system. In the present study on patients with peripheral artery disease (PAD), we correlated plasma OPG concentrations with severity of disease and the presence of cardiovascular risk factors. PATIENTS AND METHODS: Sixty-seven consecutive inpatients (26 females; mean age 70 years (S.D.: 12), undergoing percutaneous transluminal angioplasty (PTA) because of advanced symptomatic PAD of the lower extremities were studied. Severity grade of disease (clinical stage after "Fontaine", functional measurements in terms of the ankle brachial index (ABI) and "Bollinger score" of angiographies), biochemical parameters and a detailed cardiovascular risk profile were documented. Fasting plasma concentrations of OPG were measured by a commercial sandwich enzyme immunoassay. MAIN RESULTS: The mean plasma concentrations of OPG were 5.3 pmol/l (S.D.: 3.3). Plasma OPG concentrations in subjects with PAD, clinical stages III-IV (n=15) were 7.9 pmol/l (S.D.: 5.3) and were significantly higher than in patients without ischemic ulcerations (n=52; 4.6 pmol/l; S.D.: 2.0; p<0.01). The mean value of Bollinger score was 29.1 (S.D.: 19.8). OPG was positively correlated with Bollinger score of disease (r=0.31; p<0.02), age (r=0.58; p<0.01) and creatinine-values (r=0.32; p<0.01) and negatively correlated with ABI (r=-0.39; p<0.03). CONCLUSION: In patients with PAD, plasma OPG concentrations were significantly higher in subjects with ischemic ulcerations than in those without and were positively correlated with higher severity grade of disease, age and creatinine-values. Further studies are required to analyze the role of OPG as a diagnostic marker for severity of atherosclerotic disease and to assess a possible therapeutic potential as "vasculoprotegerin".

Bisphosphonate treatment does not affect serum levels of osteoprotegerin and RANKL in hypercalcemic cancer patients.

Bisphosphonates are the standard treatment for hypercalcemia of malignancy. We hypothesized that bisphosphonate treatment and the subsequent fall in serum calcium might induce changes in the RANK/RANKL/OPG system, which plays a pivotal role in the regulation of bone resorption. Soluble RANKL and OPG levels were measured in the serum of 15 hypercalcemic patients at baseline and on 5 consecutive days following treatment with the amino-bisphosphonate ibandronate. At day 0, the median soluble OPG level was elevated (p=0.0021) in the hypercalcemic group as compared to normal controls, while the median serum RANKL level was not significantly different. Ibandronate treatment and the resulting decrease (p<0.0001) in serum calcium levels did not affect the serum concentrations of OPG, serum RANKL, or the serum RANKL/OPG ratio. In comparison with day 0, these factors did not change significantly at any time-point analyzed.

Lactose intolerance: a risk factor for reduced bone mineral density and vertebral fractures?

BACKGROUND: The purpose of the present study was to determine differences, if any, in bone mineral density, the risk of fracture, and clinical behavior in patients with lactose intolerance investigated by hydrogen breath test. METHODS: The study population (n = 218; age, mean +/- SD, 58.2 +/- 11.5 years) consisted of 103 healthy individuals negative hydrogen breath test (Delta H2 0-20 ppm; group I), and 115 individuals with evidence of lactose intolerance according to the hydrogen breath test (Delta H2 > 20 ppm), of whom 40 individuals had test results of 20 ppm < Delta H2 < 59 ppm (group II). The remaining 75 individuals were strongly positive on the hydrogen breath test (Delta H2 > 60 ppm; group III). The entire study population was measured for bone mineral density in the nondominant forearm and in the vertebra (quantitative computed tomography [qCT]). Radiographs of the spine were studied for fractures. RESULTS: In healthy individuals, bone mineral density in the vertebra assessed by qCT (mean +/- SD, 111.2 +/- 31 mg/cc) did not significantly differ between those with mild (qCT, mean +/- SD, 109.8 +/- 35 mg/cc) and those with severe (qCT, mean +/- SD, 107.7 +/- 36 mg/cc) lactose intolerance. Lactose-intolerant individuals had more vertebral fractures per patient when compared with those with mild lactose intolerance or controls ( P < 0.05). Considering vertebral and self-reported non-vertebral fractures, no statistically significant differences were found. In the entire group, the overall occurrences of fracture in the presence of lactose intolerance and in controls were comparable after correction for age and body mass index (BMI). CONCLUSIONS: Individuals with lactose intolerance verified by the hydrogen breath test appear not to be at risk for accelerated bone loss. Nevertheless, a relationship between vertebral fractures and an apparent lactose intolerance cannot be excluded, as a few individuals with severe lactose intolerance had a large number of vertebral fractures.

Low bone mineral density and fragility fractures in permanent vegetative state patients.

Disuse of the musculoskeletal system causes bone loss. Whether patients in vegetative state, a dramatic example of immobilization after severe brain injury, suffer from bone loss and fractures is currently unknown. Serum markers of bone turnover, bone mineral density (BMD) measurements, and clinical data were cross-sectionally analyzed in 30 consecutive vegetative state patients of a dedicated apallic care unit between 2003 and 2007 and compared with age- and sex-matched healthy individuals. Vegetative state patients showed low calcium levels and vitamin D deficiency compared with healthy controls. Serum bone turnover markers revealed high turnover as evidenced by markedly elevated carboxy-terminal telopeptide of type I collagen (ß-crosslaps) and increased levels of alkaline phosphatase. BMD measured by dual-energy X-ray absorptiometry (DXA) scanning showed strongly decreased T- and Z-scores for hip and spine. Over a period of 5 years, 8 fragility fractures occurred at peripheral sites in 6 of 30 patients (n = 3 femur, n = 2 tibia, n = 2 fibula, n = 1 humerus). In conclusion, high bone turnover and low BMD is highly prevalent in vegetative state patients, translating into a clinically relevant problem as shown by fragility fractures in 20% of patients over a time period of 5 years. .

Influence of age and gender on associations of body mass index with bone mineral density, bone turnover markers and circulating calcium-regulating and bone-active sex hormones.

Although it is well known that body mass index (BMI) and bone mineral density (BMD) are positively correlated, the mechanisms by which adiposity reduces the risk of osteoporotic fractures are not fully understood. The present study was initiated to gain deeper insight into the mechanisms underlying the osteoprotective effect of adiposity, and to assess particularly the relevance that BMI-associated changes in circulating hormone levels could have for the build-up of additional bone mineral density. Using data from a previous study on a large cohort of healthy adult Austrians, we analyzed correlations of BMI with (i) BMD at sites in the lumbar spine and hip region, (ii) bone resorption and formation markers, (iii) circulating levels of vitamin D, parathyroid hormone, testosterone and estrogen, and (iv) rates of daily vitamin D and calcium intake. After adjustment for age, positive correlations between BMI and BMD were highly significant (P<0.0001) at all skeletal sites across the entire study cohort. Associations were stronger in post-menopausal women than in pre-menopausal women and in men. In absolute values, the gain in BMD at the lumbar spine from an incremental rise of BMI in post-menopausal women was 1.5-fold higher than in pre-menopausal women, and three times of that observed in men (P<0.05). Inverse relations between BMI and ß-crosslaps were consistently found in men (P<0.01) and in women before and after menopause (P<0.01 and P<0.05, respectively), suggesting that inhibition of osteoclastic bone resorption is responsible at least in part for the positive effect of high BMI on BMD. Sub-group analysis revealed that increasing BMI was associated with a significant fall of testosterone in men (P<0.05), and of 25-(OH)D in pre- and post-menopausal women (P<0.001 and P<0.05, respectively), but with a significant rise in PTH (P<0.01) in women before menopause. Since all these hormonal changes would cause bone loss, this excludes their playing any role in the osteoprotective effect of adiposity.

[The hormone refractory prostate cancer - a challenge for the internal specialist]. / Das hormonrefraktäre Prostatakarzinom - eine internistische Herausforderung.

Prostate cancer is the second-leading cause of cancer-related death among men and the seventh most common cause of death in the United States overall. As prostatic carcinoma is a slowly growing cancer depending on the tumor burden, use of PSA results in early cancer detection. pT2 tumors can be cured with low morbidity by radical prostatectomy. Five years after operation only few patients will experience further PSA recurrences. Adjuvant radiation therapy is effective in about half of patients with pT3 tumors in case of PSA recurrence. Most prostate cancers are androgen-dependent, meaning that they respond to androgen-ablation therapy. However, these tumors eventually become androgen-independent and grow despite androgen ablation. Since androgens are essential to the survival of prostate cells, a major question is how a prostate cell survives after androgen-ablation therapy. The mechanisms by which a prostate cancer cell survives after androgen-ablation therapy are conflicting. Specific targeting of genes involved in such pathways may further increase the chance of inventing new therapeutic options. So far, chemotherapy with docetaxel has been proved to prolong survival time and minimize cancer induced side effects in patients with hormone refractory prostate cancer.

[Systemic oncological treatment of bladder cancer]. / Onkologische Therapie des Harnblasenkarzinoms.

M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) and Cisplatin/Gemzar are potent therapies in the treatment of advanced bladder cancer. C/G provides similar efficacy in terms of overall survival compared with M-VAC, but does so with a superior safety profile. Therefore C/G is widely accepted as standard of care in locally advanced and metastatic bladder cancer. Despite potentially curative surgery almost half of the patients with muscle-invasive bladder cancer will have recurrence of disease. Based on a recent meta-analysis with data from 3005 patients, and 2 randomised studies, neoadjuvant cisplatin-containing therapy has shown to improve overall survival. Thus, the use of neoadjuvant systemic treatment should be considered state-of-the-art. The question whether adjuvant treatment will improve the outcome is still not sufficiently answered.

[Clinical relevance of biomarkers in cancer related bone disease]. / Klinische Relevanz von Biomarkern bei der Skelettmetastasierung von Malignomen.

Biomarkers as biochemical substances of collagen metabolism are produced during bone turnover and can be determined as parameters of bone metabolism not only in serum, but also in urine. These growth and decomposition products of the bone are already used to determine bone metabolism in osteoporosis and to prove efficacy of antiresorptive therapy. Metastases of the bone likewise show a higher rate of bone turnover. Nowadays detection of neoplastic bone lesions and progression of their spread are performed with x-rays, radionucleoide bone imaging and magnetic resonance imaging. In the future, biomarkers might improve early detection of bone lesions and follow-up of skeletal metastases. At present, the clinical use is documented insufficiently. In the foreseeable future the determination of the bone turnover markers and additional serum parameters of bone metabolism such as OPG, RANKL might be available for early diagnosis and follow-up in patients with bone metastatic diseases.

[Leadership strategies--the Bible as a guide to management in the health care system]. / Führungsstrategien--die Bibel als praktikables Führungsmodell im Spitalsbereich.

Management and leadership are an integral part of any organisation, to optimise procedures and increase efficiency. Aims, ideals and structures first need to be defined for tasks to be carried out successfully, particularly in difficult times. A good example for the way communities can effectively and with conviction pass on their values and standpoints from generation to generation, grow in strength and also influence their surroundings is provided by religion. This paper focuses leadership provided by charismatic personalities within the Jewish and Christian religions. Monasteries have run hospitals without governmental support ever since the Middle Ages. Leadership within today's health care system calls for a variety of strategies in the different phases of development. In times of limited resources and multifarious societies, leadership implies both a scientific as well as an ethical challenge.

Hypovitaminosis D, impaired bone turnover and low bone mass are common in patients with peripheral arterial disease.

Hypovitaminosis D is common in patients with peripheral arterial disease (PAD). Subsequent secondary hyperparathyroidism and osteomalacia contribute to bone pain and myalgias, and so aggravate clinical symptoms of claudication. We evaluated 95 out of 297 patients with angiographically confirmed PAD stages II (pain in the calves and/or thighs only during exercise) or IV (history of, or presence of local ulcers) and compared them with 44 matched healthy controls regarding their medical history, bone density measurements of the femoral neck and calcaneal bone ultrasound. Bone pain, myalgias and mobility restriction as well as routine laboratory parameters, serum vitamin D [25(OH)D], crosslaps (CTX), parathyroid hormone (PTH), osteocalcin (OC) and alkaline phosphatase (AP) were recorded and analysed. 25(OH)D was significantly lower in PAD IV patients (9.6+/-4.6 ng/ml, P<0.0001) as compared to PAD II stages and controls (19.0+/-7.6 and 19.1+/-9.1 ng/ml), paralleled by lower serum calcium [2.24+/-0.02 mmol/l, P=0.0002 versus PAD II (2.36+/-0.02) and P<0.0001 versus controls (2.39+/-0.02)] and higher iPTH serum levels (66.3+/-3.6 pg/ml, P<0.0001) as compared to PAD II patients (45.3+/-3.5) and healthy controls (38.5+/-2.4). Alkaline phosphatase and serum crosslaps values were significantly higher and age-adjusted bone density and bone ultrasound measurements significantly lower in PAD IV patients, who were also twice as likely to have bone pain and myalgias as PAD II patients. Bone ultrasound measurements correlated significantly with both clinical severity and pain as well as serological parameters of bone metabolism. Underlying PAD has a significant impact on bone density and metabolism as well as on bone and muscular pain. Patients with PAD are at high risk for osteoporosis and osteomalacia and should be regularly monitored and treated for their vitamin D deficiencies.