High resolution peripheral quantitative tomography (HR-pQCT) is used more widely to assess microarchitecture, but we are lacking comparisons between HR-pQCT and histomorphometry, which is considered the gold standard. They have only been assessed on different anatomical regions. The purpose of our study was to assess the microarchitecture and the relative contribution of cortical and trabecular bone in hip fracture with this 3D imaging technique, compared with the 2D histomorphometry.We compared the distribution of cortical and trabecular bone in the ultradistal femoral neck samples (~ 3 mm thick) obtained after total hip replacement in 21 hip osteoarthritis (HOA, 66 ± 8 yrs) and 20 hip fracture (HF, 79 ± 8 yrs) menopausal women by a direct 3D evaluation method (HR-pQCT: XtremeCT, Scanco Medical AG) and by histomorphometry, performed and averaged on three 10 μm-thick sections 800 μm apart.Significant correlations were found between both techniques for trabecular bone volume, number, thickness, separation and cortical thickness (0.51 < r′ < 0.81, p < 0.01). The connectivity was also significantly correlated (r′ = 0.58, p < 0.001) between both techniques, as well as the trabecular bone pattern factor measured in 2D with the structural model index (SMI) measured in 3D (r′ = 0.62, p < 0.001). However HR-pQCT overestimated the absolute value of most parameters, with higher values being even more overestimated. The agreement between the two techniques was weak for cortical porosity.With the 3D measurements we found that trabecular bone volume was 43% lower in HF than HOA (p < 0.01), associated with loss of trabecular connectivity (− 50%, p < 0.01) and a more rod-like structure (SMI, 22%, p < 0.01), mainly at the inferior (34%, p < 0.01) and posterior (22%, p < 0.05) quadrants. Cortical thickness was found to be lower in the posterior quadrants (− 22%, p < 0.05) and tended to be lower in HF than in HOA at the inferior quadrant (− 14%, p = 0.08), but it was still the highest at the inferior quadrant in both groups.In conclusion, 3D methods confirmed the alteration of trabecular and cortical bone found by histomorphometry in HF compared with HOA and the frequency of the rod-like structure in HF.

study [1]. When compared with placebo, histomorphometry showed high rates of bone formation and higher trabecular bone volume with no safety issues in the biopsies of patients who were treated with PTH (1–84). However, there is no information on the long-term safety and efficacy of PTH(1–84) treatment in the skeleton. We report the results of the Treatment Extension Study (TRES), which evaluated the effects of 36 months of daily PTH(1–84) treatment. Methods: 99 patients who had completed 18 months of daily placebo treatment together with daily vitamin D3 (400 IU) and calcium (700 mg) in the TOP study and 18 months of daily PTH(1–84) with or without calcium in the Open Label Extension Study (OLES) were enrolled and continued on the same open label regimen for another 18 months in TRES. There were no placebo-treated patients in TRES. The ITT population for TRES comprised 91 patients and there was an interruption in PTH treatment between OLES and TRES of ∼2 months. Evaluable iliac crest biopsies were collected from 14 patients (none of whom had provided a biopsy previously) after 36 months of PTH(1–84) treatment. Results: There were no histopathological abnormalities in cancellous or cortical bone with PTH(1–84) treatment. This included an absence of osteomalacia, marrow fibrosis or dyscrasias, woven bone, abnormal osteoid, or cortical trabecularisation. Cortical porosity was 5.6%, the same as observed at 18 months in TOP. Measures of cancellous, periosteal and endocortical bone formation were similar to those at 18 months. Structural variables, including trabecular bone volume, number, thickness and cortical thickness were generally similar to or slightly lower than corresponding bone biopsies obtained from patients following 18 months of PTH therapy. Conclusion: Daily treatment of postmenopausal osteoporotic women with PTH(1–84) for 36 months was generally safe and biopsies showed that cancellous and cortical bone appeared entirely normal. The consistency of the biopsy results following 18 and 36 months of PTH treatment suggests that long-term therapy with PTH preserves the initial benefits accrued during initial exposure. 1. Recker RR, et al. Bone 2009;44:113-9. Conflict of interest: None declared.

Aim: The aim of our study was to investigate whether the administration of rosiglitazone affects bone metabolism and risk of fracture in patients with T2D. Methods: We have investigated 23 patients (9 males and 14 females) with T2D from age 38 to age 51. Patients were divided in two groups: in group I patients previously treated with diet alone were included, in group II — patients who received medications of sulfanilurea. Patients in both groups were prescribed to rosiglitazone 2 mg/d for 20 weeks. We measured HbA1c, fasting and postprandial glucose, ionized calcium (Ca), phosphorus values, parathyroid hormone (PTH), osteocalcin (OC). Bone mineral density was measured by dual-energy X-ray absorptiometry. Results: Rosiglitazone treatment was followed by decreased levels of OC (7.2±0.2 ng/ml, p<0.01). We have not revealed significant changes in bonemineral density in patients treatedwith rosiglitazone. There were no significant changes in levels of Ca (from 1.18± 0.01 mmol/l to 1.09±0.01 mmol/l) and PTH (from 38.3±0.01 pg/ml to 41.7±0.01 pg/ml). Conclusion: Rosiglitazone treatment was followed by decreased level of bone turnover. Conflict of interest: None declared.

Muscle weakness, neuro-muscular deficits, balance and gait disorders are manifestations of mobility impairment and increase the risk of "intrinsic"falls. Fallings in old age break bones, fear of falling reduces self-esteem and physical activities and this initiates a vicious circle of de-conditioning. Fractures are also the relevant outcome of osteoporoses, but more than 90 % of hip fractures are fall-related. D-hormone (1,25[OH](2) D; calcitriol), the active vitamin D metabolite, and its receptor (VDR) play an important role in muscle development. Older age is significantly associated with decreased VDR expression in human skeletal muscle tissue as well as with D-hormone dependent changes in muscle fibre type and muscle cell differentiation and metabolism. A positive correlation was found between femoral muscle power and -function and D-hormone serum levels in elderly women and men. This interaction was strongly supported by the recently shown fact, that higher D-hormone serum levels are correlated with lower fall rates in elderly women. All these results together suggest that the age-related increase of falls seemed in part to be explained by a decrease of Dhormone and VDR.Impaired renal function is detrimental to the activation of D-hormone and may be in future a diagnostic tool for identifying patients with decreased bone mineral density and muscle power, increased risk of falls and fractures. Histochemical classification based on muscle biopsies revealed that a six months treatment with 1 ug alfacalcidol daily increased the number and the diameter of fast-twitch type II A fibres. In elderly osteopenic women calcitriol was able to delay the decline of physical performance tests. A significant decrease in the fall rate after three years of treatment with 0.5 ug calcitriol daily in communitydwelling osteopenic women without vitamin D deficiency and especially with reduced kidney function has been described. Alfacalcidol, an advantageous pro-drug of calcitriol, has demonstrated after nine months therapy the reduction of falls by 50-70% in elderly, community-dwelling women and men with normal vitamin D levels in serum and who have taken more than 500 mg calcium daily from diet or had a creatinine clearance of less than 65 ml/min. Metaanalyses on the basis of controlled, randomised clinical trials with alfacalcidol and calcitriol have shown the higher reduction of falls, vertebral and non-vertebral fractures versus plain vitamin D.The pleiotropic effects of alfacalcidol on reduced calcium metabolism in muscles, on the regulation on muscle fibre composition, on decreased muscle function and neuro-muscular co-ordination are unique, and thus differentiate this form of therapy from all other anti-osteoporotic drugs. The rationale of the advantage of alfacalcidol versus plain vitamin D is the fact that this drug is acting without metabolic activation in the kidney which results in higher concentrations of D-hormone at the target organs, e. g. muscles, nerves, brain, and in more local expression of VDR. Plain vitamin D seemed to be active mainly in vitamin D deficient patients with normal kidney function.

Aluminium-containing phosphate binders were replaced by a calcium and magnesium carbonate-containing antacid in 20 patients on long-term haemodialysis, over a three-month period in all of them, for 12 months in ten. After two months the serum aluminium level fell (mean +/- SD) from 3.0 +/- 1.6 to 1.4 +/- 0.5 mumol/l (P less than 0.001). After three months the serum phosphate level had fallen from 1.8 +/- 0.4 to 1.5 +/- 0.4 mumol/l (P less than 0.05), while during the same period parathormone (PTH-NH2) fell from 1.4 +/- 1.4 to 0.8 +/- 0.7 ng/ml (P less than 0.05). Serum total calcium concentration rose after two months from 2.2 +/- 0.2 to 2.4 +/- 0.2 mmol/l (P less than 0.001). In a third of patients the uraemic acidosis was corrected, standard bicarbonate rising from 18 +/- 2 to 21 +/- 3 mmol/l (P less than 0.05). Serum pH, potassium, sodium, magnesium and alkaline phosphatase did not change significantly. Hypercalcaemia was an expected disadvantage: repeated symptom-free episodes of hypercalcaemia occurred in six of 20 patients during the first three months and in a further two up to 12 months. These episodes were successfully controlled by a reduction of CaCO3/MgCO3 dosage and readministration of Al(OH)3. Extraosseous calcifications were not observed.

Multiple myeloma is a fatal hematologic malignancy associated with clonal expansion of malignant plasma cells within the bone marrow and the development of a destructive osteolytic bone disease. The principal cellular mechanisms involved in the development of myeloma bone disease are an increase in osteoclastic bone resorption, and a reduction in bone formation. Myeloma cells are found in close association with sites of active bone resorption, and the interactions between myeloma cells and other cells within the specialized bone marrow microenvironment are essential, both for tumor growth and the development of myeloma bone disease. This review discusses the many different factors which have been implicated in myeloma bone disease, including the evidence for their role in myeloma and subsequent therapeutic implications.

Purpose:  To evaluate if osteonecrosis diagnosed on MR images of the knee relates to reduced bone mineral density (BMD) and may be caused by an insufficiency fracture. Material and Methods:  Thirty-two consecutive patients (8 men, 24 women; age range 27–82 years, mean 62 years) with MR findings of osteonecrosis of the femoral or tibial condyle were prospectively included. Trabecular and cortical BMD were measured with high resolution peripheral quantitative CT in the non-dominant distal radius and the tibia of the involved extremity. One tibia was not measured due to posttraumatic deformity. Results:  The mean trabecular BMD of the radius was 81% of the young-adult average peak BMD (range 19–160%). The mean cortical BMD in the radius was 86% (range 63–108%). The mean trabecular BMD in the tibia was 92% (range 28–160%). The mean cortical BMD in the tibia was 86% (range 49–132%). The values of the trabecular bone of the distal radius (tibia) were normal in 11 (15) patients, osteopenic in 12 (4), and osteoporotic in 9 (12), respectively. The cortical bone values of the distal radius (tibia) were normal in 12 (13) patients, osteopenic in 12 (12), and osteoporotic in 8 (6), respectively. Conclusion:  Osteoporosis and osteopenia are commonly found in patients with osteonecrosis of the knee as diagnosed on MR images. This indicates that for some patients an insufficiency mechanism may be responsible for the MR findings. However, in the patients with normal bone density other reasons for osteonecrosis may be present.

: The current study was designed to investigate the rate of bone loss in distal radius and its association with baseline volumetric bone mineral density (BMD) and years since menopause (YSM) in peri- and postmenopausal women using precise and multislice peripheral quantitative computed tomography (pQCT; Densiscan 2000). Two hundred and five healthy Hong Kong Chinese perimenopausal ( n = 26) and postmenopausal ( n = 179) women within 10 years of the onset of menopause were recruited. Anthropometric parameters and menstrual status were also measured. The linear regression model derived from the baseline volumetric BMD revealed a significant and slightly better correlation with YSM than age, with a YSM-related annual decline of 2.56%, 1.82% and 0.65% in trabecular BMD (tBMD), integral BMD (iBMD) and cortical BMD (cBMD), respectively. Follow-up measurements after a time interval of 12 months showed that the rate of bone loss was higher than the annual decline in BMD calculated from the baseline BMD, with decreases of 2.89%, 2.16% 0.91% in tBMD, iBMD and cBMD, respectively. Baseline BMD was associated with age or YSM ( r ranges from −0.283 to −0.502; p <0.001 in all cases), but no relationship was found between annual rate of bone loss and age or YSM. The rate of bone loss did not correlate with baseline volumetric BMD values or YSM after dividing the subjects into fast bone losers (with annual tBMD loss ≥3%), normal bone losers (with annual tBMD loss ≥ 1% but <3%) or slow bone losers (with annual tBMD loss <1%). The rate of bone loss was greater in both trabecular and cortical bone of postmenopausal women within the first 3 menopausal years but was only significant in the iBMD as compared with perimenopausal and postmenopausal women over 7 years after onset of menopause. The percentage distribution of slow and fast bone losers was not found to be associated with YSM. As a total of only 4 fracture cases were documented, the study could not provide conclusive information on whether perimenopausal and early postmenopausal baseline volumetric BMD or rate of bone loss determines the development of osteoporosis or fracture occurrence.

To examine whether changes in autonomic activity have an effect on the latency of the vagally mediated cardiac baroreflex response in humans, we investigated the effects of neck suction fluctuating sinusoidally at 0.2 Hz on R-R intervals (known to be mediated mainly by vagal activity) in the supine position, during 15 degrees head-down tilt and 60 degrees head-up tilt, and during vagotonic (2 microg/kg) and vagolytic (10 microg/kg) doses of atropine while the subjects breathed at 0.25 Hz. The phase shift between fluctuations in neck chamber pressure and in R-R interval was calculated by complex transfer function analysis and was used as a measure of the time delay between carotid baroreceptor stimulation and cardiac effector response. Cardiac baroreflex responsiveness increased significantly during low-dose atropine and decreased during head-up tilt or 10 microg/kg atropine. With increasing tilt angle, the time delay between cyclic baroreceptor stimulation and oscillations in R-R interval increased from 0.32 +/- 0.27 s (head down), to 0.59 +/- 0.25 s (supine position, P < 0.05 vs. head down), and to 0.86 +/- 0.27 s (head up, P < 0.01 vs. supine). Low-dose atropine had a similar effect to head-down tilt on baroreflex latency, whereas 10 microg/kg atropine increased the time delay markedly to 1.24 +/- 0.30 s. Our results demonstrate that changes in autonomic activity, generated either by gravitational stimulus or by atropine, not only affect baroreflex responsiveness but also have a major influence on the latency of the vagally mediated carotid baroreceptor-heart rate reflex. The prolonged baroreflex latency during decreased parasympathetic function may contribute to an unstable regulation of heart rate in patients with cardiac disease.