We describe a sinus, referred to as a bone remodeling compartment (BRC), which is intimately associated with cancellous bone remodeling. The compartment is lined on its marrow side by flattened cells ...and on its osseous side by the remodeling bone surface, resembling a roof of flattened cells covering the bone surface. The flat marrow lining cells are in continuity with the bone lining cells at the margins of the BRC. We examined a large number of diagnostic bone biopsy specimens received during recent years in the department. Furthermore, 10 patients (8 women and 2 men, median age 56 40–69 years) with the high turnover disease of primary hyperparathyroidism who were treated with parathyroidectomy and followed for 3 years were included in the histomorphometric study. Bone samples for the immuno‐enzyme staining were obtained from an amputated extremity of child. The total cancellous bone surface covered by BRC decreases by 50% (p < 0.05) following normalization of turnover and is paralleled by a similar 50% decrease in remodeling surface (p < 0.05). The entire eroded surface and two‐thirds of the osteoid surface are covered by a BRC. BRC‐covered uncompleted walls are 30% (p < 0.05) thinner than those without a BRC. This indicates that the BRC is invariably associated with the early phases of bone remodeling, that is, bone resorption, whereas it closes during the late part of bone formation. Immuno‐enzyme staining shows that the flat marrow lining cells are positive for alkaline phosphatase, osteocalcin, and osteonectin, suggesting that they are bone cells. The first step in cancellous bone remodeling is thought to be the lining cells digesting the unmineralized matrix membrane followed by their disappearance and the arrival of the bone multicellular unit (BMU). We suggest that the lining cell barrier persists during bone remodeling; that the old lining cells become the marrow lining cells, allowing bone resorption and bone formation to proceed under a common roof of lining cells; that, at the end of bone formation, new bone lining cells derived from the flattened osteoblasts replace the marrow lining cells thereby closing the BRC; and that the two layers of lining cells eventually becomes a single layer. The integrity of the osteocyte‐lining cell system is reestablished by the new generation of lining cells. The BRC most likely serves multiple purposes, including efficient exchange of matrix constituents and minerals, routing, monitoring, or modulating bone cell recruitment, and possibly the anatomical basis for the coupling of bone remodeling.
Objectives. Statin drugs act as inhibitors of the 3-hydroxy-3methylglutaryl coenzyme A (HMG-CoA) reductase enzyme early in the mevalonate pathway, thereby reducing the endogenous cholesterol ...synthesis. In recent studies, it has been suggested from epidemiological data that statins also may improve vitamin D status, as measured by increased plasma 25-hydroxyvitamin D (25OHD) levels. We now report the results from a randomised controlled trial on effects of simvastatin on plasma 25OHD levels. Design and Methods. We randomised 82 healthy postmenopausal women to one year of treatment with either simvastatin 40 mg/d or placebo and performed measurement at baseline and after 26 and 52 weeks of treatment. The study was completed by 77 subjects. Results. Compared with placebo, plasma levels of cholesterol and low-density lipoproteins decreased in response to treatment with simvastatin, but our study showed no effect of simvastatin on vitamin D status. However, plasma levels of triglycerides were inversely associated with tertiles of plasma 25OHD levels and changes in plasma triglycerides levels correlated inversely with seasonal changes in vitamin D status. Conclusion. Our data do not support a pharmacological effect of statins on vitamin D status, but do suggest that vitamin D may influence plasma lipid profile and thus be of importance to cardiovascular health.
Purpose The objective of this study was to address whether among people living in Denmark, those treated with medications to prevent osteoporosis have an increased risk for inflammatory jaw disease ...compared with those not treated. Patients and Methods A historical cohort study was designed to compare the rate of inflammatory jaw-related events, ie, osteomyelitis, osteitis, periostitis, or sequestrum, between Danish patients who had been prescribed oral bisphosphonates (BP) and other drugs for the treatment of osteoporosis between 1996 and 2006 (the exposed group), and a random sample of the Danish population drawn from a nationwide registry who had not been prescribed oral BPs or other medications to treat osteoporosis (the nonexposed group). The nonexposed subjects were age- and gender-matched to the exposed subjects and randomly drawn from the general population at a ratio of 3 non-BP subjects to 1 BP subject. The primary explanatory variable was oral BP exposure status. Associations between BP treatment and inflammatory jaw events were ascertained using hazard ratios (HR) Cox proportional hazards models. Results The study sample was composed of 103,562 index subjects and 310,683 control subjects. After adjusting for other factors, including diabetes and chemotherapy, alendronate (HR = 3.15, 95% confidence interval 1.44-6.87) and etidronate (HR = 2.23, 95% confidence interval 1.15-4.31) were associated with an increased risk for inflammatory jaw events. There was no association between oral BP dose and risk for inflammatory jaw events. Conclusion The oral BPs alendronate and etidronate were associated with an increased risk for inflammatory jaw events.
Summary
Background Vitamin D insufficiency is very common and is known to cause secondary hyperparathyroidism (SHPT). However, in some subjects the PTH response to low vitamin D levels is blunted, ...which has been termed functional hypoparathyroidism (FHPT).
Aim We compared indices of calcium homeostasis, bone metabolism and body composition in subjects with differential PTH responses to low vitamin D levels.
Design Cross‐sectional study. In 405 recent postmenopausal women with vitamin D insufficiency, we compared levels of bone turnover markers, bone mineral density (BMD), body composition, and body weight between subjects with SHPT and FHPT.
Results Plasma 25‐hydroxyvitamin D (P‐25OHD) levels were slightly higher (P < 0·05) in SHPT compared with FHPT. SHPT was associated with higher levels of osteocalcin and bone‐specific alkaline phosphatase, whereas whole body BMD and hip‐ and lumbar spine‐BMD were significantly reduced. Subjects with SHPT had a 7% (P < 0·01) higher body weight and a 23% higher fat mass (P < 0·01) than subjects with FHPT, whereas lean tissue mass did not differ between groups. In SHPT, fat mass was increased by 14% (P < 0·001) at the upper and lower extremities and by 33% (P < 0·001) at the trunk. In a regression model, significant predictors of fat mass was P‐PTH (rp = 0·248, P < 0·01) and P‐osteocalcin (rp = –0·115, P = 0·02), with no effects of P‐25OHD or P‐creatinine levels.
Conclusions Effects of vitamin D insufficiency on bone is associated with the PTH responses. The increased body weight and fat mass in SHPT compared with FHPT may imply that PTH excess contributes to fat accumulation.
We studied the effects of increasing age, dosage, and duration of parathyroid hormone (PTH) treatment on changes in bone mineral density (BMD). Randomized placebo controlled trials on PTH treatment ...in men or women were retrieved from PubMed (1951 to present), Web of Science (1945 to present), or Embase (1974 to present). The search date was November 16, 2010. All studies comparing PTH treatment to either placebo or antiresorptive drugs—for example, bisphosphonates or hormone replacement therapy—were included. A total of 214 studies were identified in the initial search, and 15 of these trials were included. By metaregression analysis, we found that the increase in spine BMD (
Z
-score) after PTH treatment was blunted by increasing age (
R
2
= 0.27; 2
p
= 0.01, slope −0.023
Z
-scores per year, 11 studies). By increasing PTH dosage (μg/d), spine BMD increased significantly (2
p
= 0.002) with a slope of +0.011
Z
-scores/μg/d of teriparatide. Furthermore, the duration of treatment was positively correlated to spine BMD (
P
< 0.001) with a slope of +0.043
Z
-score for each extra month of treatment. We evaluated the BMD effect in hips and found no age dependency (
R
2
= 0.04;
P
= 0.66; 8 studies). However, for the spine, we found a significant relation to daily dosage (
P
= 0.011),
Z
-score coefficient 0.0051 ± 0.0020 (2
p
< 0.01). The treatment duration also correlated positively by a
Z
-score coefficient of 0.0170 ± 0.0053, 2
p
< 0.01 per extra month of treatment. PTH treatment alone seems to be able to improve BMD significantly. However, the BMD increase was significantly lower with increasing age in the spine. No age dependency was observed in the hips. In general the effect of treatment was improved with increasing dosage and duration of treatment from 6 to 36 months.
Background. Studies on bone effects of long-term substitution therapy with levothyroxine (LT4) have shown discrepant results. Previous studies have, however, not evaluated volumetric bone mineral ...densities (vBMD), bone structure, and strength using high resolution peripheral quantitative computed tomography (HR-pQCT) and finite element analysis (FEA). Using a cross-sectional design, we aimed to determine whether BMD, structure, and strength are affected in hypothyroid patients on LT4 substitution therapy. Methods. We compared 49 patients with well-substituted hypothyroidism with 49 age- and gender-matched population based controls. Areal BMD was assessed by DXA, vBMD and bone geometry by HR-pQCT, and bone strength by FEA. Results. Patients had been thyroidectomized due to thyroid cancer (10%) and nontoxic (33%) or toxic goiter (57%). 82% were women. TSH levels did not differ between groups, but patients had significantly higher levels of T4 (p<0.001) and lower levels of T3 (p<0.01). Compared to controls, patients had higher levels of magnesium (p<0.05), whereas ionized calcium and PTH were lower (p<0.05). Bone scans did not reveal any differences in BMD, bone geometry, or strength. Conclusion. If patients with hypothyroidism are well-substituted with LT4, the disease does not affect bone indices to any major degree.
Prior studies have indicated an excess risk of gastroduodenal ulcers and esophagus perforations with the use of bisphosphonates. However, little is known about the contribution of comorbid conditions ...and concomitant drug use on this risk. We studied the risk of esophagus and gastric events in patients on a wide range of drugs against osteoporosis both before and after initiation of these drugs. We studied a nationwide register-based cohort from Denmark with all users of drugs against osteoporosis between 1996 and 2006 (
n
= 103,562) as cases and three age- and sex-matched controls from the general population (
n
= 310,683). In a crude analysis, most drugs were already associated with an increased risk of esophagitis, esophageal ulcerations, or esophageal perforations or gastroduodenal ulcers before initiation of the drugs. Upon adjustment, this excess risk disappeared for most drugs except parathyroid hormone and its analogues, etidronate and clodronate. Only for etidronate, alendronate, and raloxifene were sufficient data present for events after initiation of the drugs, and for these, an increased risk was present for all events except gastroduodenal ulcers with raloxifene. Several drugs against osteoporosis are associated with an increased risk of esophagitis, esophageal ulcers, esophageal perforation, and gastroduodenal ulcers. However, the increase was already present before initiation of the drug for several types of drugs against osteoporosis. This points at an effect of the underlying condition being treated or comorbid conditions and drugs being provided in patients with osteoporosis, such as nonsteroidal anti-inflammatory drugs and corticosteroids.
Extended physical inactivity causes disuse osteoporosis in humans. In contrast, brown bears (Ursus arctos) are highly immobilised for half of the year during hibernation without signs of bone loss ...and therefore may serve as a model for prevention of osteoporosis.
To study 25-hydroxy-vitamin D (25OHD) levels and bone turnover markers in brown bears during the hibernating state in winter and during the active state in summer. We measured vitamin D subtypes (D₂ and D₃), calcitropic hormones (parathyroid hormone PTH, 1,25-dihydroxy-vitamin D 1,25(OH)₂D) and bone turnover parameters (osteocalcin, ICTP, CTX-I), PTH, serum calcium and PIIINP.
We drew blood from seven immobilised wild brown bears during hibernation in February and in the same bears while active in June.
Serum 25-hydroxy-cholecalciferol (25OHD₃) was significantly higher in the summer than in the winter (22.8±4.6 vs. 8.8±2.1 nmol/l, two tailed p-2p = 0.02), whereas 25-hydroxy-ergocalciferol (25OHD₂) was higher in winter (54.2±8.3 vs. 18.7±1.7 nmol/l, 2p<0.01). Total serum calcium and PTH levels did not differ between winter and summer. Activated 1,25(OH)₂D demonstrated a statistically insignificant trend towards higher summer levels. Osteocalcin levels were higher in summer than winter, whereas other markers of bone turnover (ICTP and CTX-I) were unchanged. Serum PIIINP, which is a marker of connective tissue and to some degree muscle turnover, was significantly higher during summer than during winter.
Dramatic changes were documented in the vitamin D₃/D₂ ratio and in markers of bone and connective tissue turnover in brown bears between hibernation and the active state. Because hibernating brown bears do not develop disuse osteoporosis, despite extensive physical inactivity we suggest that they may serve as a model for the prevention of this disease.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Quantitative computed tomography (QCT) is considered to measure true volumetric bone mineral density (vBMD; mg/cm3) and enables differentiation between cortical and trabecular bone. We aimed to ...determine the value of QCT by correlating areal BMD (aBMD) by dual-energy X-ray absorptiometry (DXA) with vBMD when using a fixed threshold to delineate cortical from trabecular bone. In a cross-sectional study, 98 postmenopausal women had their hip scanned by DXA and by QCT. At the total hip and the trabecular bone compartment, aBMD correlated significantly with vBMD (r=0.74 and r=0.63; p<0.01, respectively). A significant inverse correlation was found between aBMD and cortical vBMD (r=-0.57; p<0.01). Total hip volume by QCT did not change with aBMD. However, increased aBMD was associated with a decreased trabecular bone volume (r=-0.36; p<0.01) and an increased cortical volume (r=0.69; p<0.01). Changing the threshold used to delineate cortical from trabecular bone from default 350 mg/cm3 to either 300 or 400 mg/cm3 did not affect integral vBMD (p=89) but had marked effects on estimated vBMD at the cortical (p<0.001) and trabecular compartments (p<0.001). Furthermore, increasing the threshold decreased cortical thickness (p<0.001), whereas the strength parameter in terms of buckling ratio increased (p<0.001). Our results show good agreement between aBMD and integral vBMD. However, using a fixed threshold to differentiate cortical from trabecular bone causes an apparent increase in cortical volume with a decrease in cortical density as aBMD increases. This may be caused by the classification of a larger part of the transition zone as cortical bone with increased aBMD.
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