Structural progression rate decreases over time on serial radiography and magnetic resonance imaging of sacroiliac joints and spine in a five-year follow-up study of patients with ankylosing spondylitis treated with tumour necrosis factor inhibitor.

OBJECTIVE: To investigate temporal changes in structural progression assessed by serial conventional radiography and magnetic resonance imaging (MRI) of the sacroiliac joints (SIJs) and spine in patients with ankylosing spondylitis (AS) treated with tumour necrosis factor (TNF) inhibitor for 5 years. METHOD: Forty-two patients were included and 33 patients were followed for 5 years in a prospective investigator-initiated study. Conventional radiographs were required four times and MRI seven times. The modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS); Spondyloarthritis Research Consortium of Canada (SPARCC) MRI SIJ and Spine Inflammation, and SPARCC MRI SIJ Structural Score (SSS) for Fat, Erosion, Backfill, and Ankylosis; and the Canada-Denmark MRI scores for Spine Inflammation, Fat, Erosion, and New Bone Formation (NBF) were applied. RESULTS: Compared with baseline, MRI Inflammation had decreased significantly at week 22 (spine)/week 46 (SIJ) and thereafter. MRI SIJ Fat (from week 22), SIJ Ankylosis, Spine NBF, and mSASSS had increased significantly at week 46 and thereafter. SIJ Erosion had decreased from year 2. The annual progression rate in mSASSS was significantly higher during weeks 0-46 compared to week 46 to year 3. In multivariate regression analyses, baseline SIJ Inflammation and Backfill were independent predictors of 5 year progression in SIJ Ankylosis. Spine Erosion predicted progression in Spine NBF. Longitudinally, Ankylosing Spondylitis Disease Activity Score, Bath Ankylosing Spondylitis Disease Activity Index, MRI Spine Inflammation, Fat, and Erosion scores were significantly associated with mSASSS. SIJ Inflammation, Fat, Erosion, and Backfill scores were longitudinally associated with SIJ Ankylosis. Structural progression was not associated with body mass index, smoking, or Assessment of SpondyloArthritis international Society Non-Steroidal Anti-Inflammatory Drug Index. CONCLUSION: In a 5 year follow-up study of patients with AS treated with TNF inhibitor, structural progression decreased over time.

Bone minerals changes in obese women during a moderate weight loss with and without calcium supplementation.

A significant relationship between body weight (BW) and bone mass (BM) has been established previously. A diet-induced weight loss is accompanied by a significant decrease in bone mineral density (BMD) and total body bone mineral (TBBM), but the underlying mechanisms are not clarified. Sixty-two obese women were included in the study. Dual-energy X-ray absorptiometry (DXA) and measurements of a series of calcium-regulating hormones and biochemical markers of bone turnover were performed at baseline and after 1 month and 3 months on a low calorie diet. Thirty of the women were randomized to a daily supplement of 1 g of calcium. After an additional 3 months without dietary prescriptions or calcium supplements, a subgroup of 48 subjects (24 from each group) were scanned again using DXA. There was a significant decrease in TBBM after 1 month and 3 months. A similar pattern was observed in the bone mineral content (BMC) of the lumbar spine in the patients who did not receive a calcium supplement, whereas no changes occurred in the supplemented group. The initial calcium supplementation seemed to protect against bone loss in the lumbar spine but not in the TBBM. In the nonsupplemented group, a statistically significant inverse correlation was found between the calcium/creatinine ratio in the morning urine and the changes in BMC of the lumbar spine. Such a relationship was not seen in the calcium-supplemented group. In the nonsupplemented group, no significant biochemical changes were observed, whereas a significant decrease in serum parathyroid hormone (PTH) was seen in the calcium-supplemented group. This might explain some of the protective effects of calcium supplementation on trabecular bone mass. We conclude that a diet-induced weight loss is accompanied by a generalized bone loss, which probably is explained mainly by a reduced mechanical strain on the skeleton. This loss can be partly inhibited by a high calcium intake. Therefore, a calcium supplementation should be recommended during weight loss, even if the diet contains the officially recommended amounts of calcium.

Effects of growth hormone and insulin-like growth factor I in men with idiopathic osteoporosis.

Injections with growth hormone (GH) or insulin-like growth factor I (IGF-I) have been proposed for anabolic therapy in osteoporosis. In a cross-over study, 12 men with idiopathic osteoporosis received daily subcutaneous injections of GH (2 IU/m2) or IGF-I (80 micrograms/kg) for 7 days with 12 weeks of wash-out. Serum levels of procollagen type I increased by 29% following treatment with GH (P < 0.001) and by 43% with IGF-I (P < 0.001 compared with pretreatment levels; P < 0.05 compared with GH injections), whereas both treatments rendered a 20% increase in osteocalcin concentrations (P < 0.001), indicating enhanced bone formation. There was also evidence of stimulated bone resorption, as the urinary levels of deoxypyridinoline increased by 44% following GH injections (P < 0.001) and by 29% following IGF-I (P < 0.001), and there were 28% higher serum concentrations of IGF-I after GH than after IGF-I injections. Although markers of bone metabolism increased under both treatments, comparison of the treatments suggests that IGF-I enhanced formation of collagen type I more than did GH. Furthermore, the stimulation of bone resorption was detected as soon as 4 days after the initiation of GH injections. Some of the differences might be dose-dependent, but could also indicate separate mechanisms at the cellular level.

Effect of nasal salmon calcitonin on bone remodeling and bone mass in postmenopausal osteoporosis.

The effect of nasal salmon calcitonin (SCT) on bone has been investigated by densitometry, biochemical markers of bone turnover, and histomorphometry. 62 women (mean age 65 years) who had experienced Colles' fracture after menopause were randomized to receive either nasal salmon calcitonin (SCT) 200 IU or nasal placebo daily for 24 months. All received a daily supplement of 0.5 g calcium. There was a significant increase above baseline in the bone mineral density of the lumbar spine in the SCT group (2.5%; 95% confidence interval 0.9--4.2%) and in the placebo group (1.7%; 95% confidence interval 0.3--3.1%) after 24 months, but the difference between the groups was not significant (0.8%; 95% confidence interval -1.2-3.0%). Serum levels of osteocalcin decreased significantly below baseline in the SCT group, whereas they were unchanged in the placebo group. At months 12 and 24, serum levels of osteocalcin were significantly lower in the SCT group than in the placebo group (p < 0.03). Urinary levels of deoxypyridinoline/creatinine decreased significantly below baseline in the SCT group, whereas only a transient decrease was observed in the placebo group. The differences between the groups were, however, not significant. The erosion depth was significantly lower in the SCT group than in the placebo group after 12 months (median [interquartile range]; 46.9 mu m [10.4] vs. 50.5 mu m [10.7]; p = 0.03), whereas bone volume and activation frequency did not differ between the groups. This study indicates that nasal SCT in a dose of 200 IU daily induces only a minor inhibition of bone resorption and therefore produces only a minor increase in bone mass. Furthermore, it seems that nasal SCT in a dose of 200 IU does not interfere with the recruitment of new bone multicellular units, but preferably decreases ongoing osteoclastic bone resorption.

Short-term growth and collagen turnover in asthmatic adolescents treated with the inhaled glucocorticoid budesonide.

Short-term lower leg growth, the insulin-like growth factor axis, and collagen turnover were assessed in 16 adolescents with asthma during treatment with inhaled budesonide, 800 micrograms/d, from a pressurized metered dose inhaler with a volume spacer. The design was a randomized double blind, placebo-controlled two-period crossover trial with treatment periods of 4 weeks and a 1-week wash-out. Lower leg growth was assessed by knemometry. Serum levels of insulin-like growth factor-I, insulin-like growth factor-binding protein-3, and the following markers of collagen turnover were evaluated: Serum markers of type I collagen formation and degradation; the carboxy-terminal propeptide of type I procollagen and the carboxy terminal pyridinoline cross-linked telopeptide of type I procollagen (ICTP), the serum marker of type III collagen formation; the amino-terminal propeptide of type III procollagen (PIIINP) and the urinary concentrations of the type I collagen degradation products pyridinoline (PYD) and deoxypyridinoline (DPD) cross-links. Mean lower leg growth velocity was suppressed from 0.51 mm/week during placebo to 0.18 mm/week during budesonide treatment (p < 0.001). No statistically significant effects on insulin-like growth factor-1, insulin-like growth faster-binding protein-3, or carboxy-terminal propeptide of type I procollagen were observed. ICTP and PIIINP were reduced with 2.3 and 2.5 micrograms/liter (p < 0.001 and p < 0.001, respectively) during budesonide treatment, urinary concentrations of PYD and DPD with 32.9 nmol/mmol creatinine (p < 0.005) and 6.8 nmol/mmol creatinine (p < 0.005), respectively. Significant correlations between lower leg growth velocity and ICTP, PIIINP, PYD, and DPD during placebo (p < 0.01, p < 0.05, p < 0.01, and p < 0.01) and budesonide (p < 0.05, p < 0.05, p < 0.05, and p < 0.05) periods were found. Short term lower leg growth suppression in adolescents treated with inhaled budesonide, 800 micrograms/d, reflects suppression of type I and III collagen turnover.

Osteoporosis: a risk factor in periodontal disease.

Osteoporosis is suspected as a risk factor in periodontal disease, but previous studies have failed to establish a relationship. Possible explanations for this could be lack of precise methods for assessment of osteoporosis in the jaws and confounding of the result by other factors such as age, gender, or smoking. In the present study 12 female patients with osteoporotic fractures (Group O) and 14 normal women (Group N) were examined clinically for plaque (VPI), gingival bleeding (GBI), and loss of attachment on the 6 Ramfjord index teeth. Bone mineral content (BMC) of the mandible and forearm was determined by dual photon scanning. Results were presented as arithmetic means +/- standard error, and differences between groups were tested by 2-sample t-test. The two groups were comparable with respect to age (O: 68.3 +/- 1.8 years, N: 68.1 +/- 1.5 years), menopausal age (O: 47.5 +/- 1.8 years, N: 47.2 +/- 1.3 years), and smoking habits (O: 4 smokers, N: 3 smokers). The osteoporotic women had significantly lower BMC values than controls in the mandible (O: 0.63 +/- 0.04 in U/cm2; N: 0.78 +/- 0.02 in U/cm2, P < 0.01) and forearm (O: 1.05 +/- 0.05 in U/cm; N: 1.28 +/- 0.05 in U/cm, P < 0.01). No significant differences were found with respect to plaque (O: 46.67 +/- 10.00%, N: 36.67 +/- 6.67%) and gingival bleeding (O: 46.67 +/- 11.67%, N: 43.33 +/- 10.00%), whereas significantly greater loss of attachment was seen in osteoporotic women (O: 3.65 +/- 0.18 mm, N: 2.86 +/- 0.19 mm, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Intraindividual variability in bone markers in the urine.

The biological variability of urinary bone resorption markers was measured in 30 healthy and 20 postmenopausal osteoporotic women. The second spot urines were collected at weekly intervals for 5 weeks and urinary pyridinium crosslinks, hydroxyproline, calcium and Ntx were evaluated. Results are discussed in relation to analytical variability, critical difference values and index of individuality. In conclusion monitoring and classifying bone turnover in groups of persons are well established, but the routine use of urinary biochemical bone markers in the individual patient is of limited use.

[Chylous ascites in adults. A review of etiology, physiopathology, diagnostic methods and therapeutic possibilities]. / Chyloascites hos voksne. En oversigt over aetiologi, patofysiologi, diagnostiske procedurer og behandlingsmuligheder.

Chylous ascites is an unusual condition. Many causes, usually malignancy, are responsible. In the present article, the authors define chylous ascites, describe the pathological physiology, etiology, diagnostic procedures and management. The case of a man aged 74 years with chylous ascites on account of malignant lymphoma in the retroperitoneum is presented.

Symptomatic osteoporosis: a risk factor for residual ridge reduction of the jaws.

The purpose of this study was to clarify if symptomatic osteoporosis is a risk factor for severe residual ridge reduction of the jaws. The analysis included 12 edentulous women with osteoporotic fractures, otherwise normal, and 16 normal edentulous women matched with respect to age, menopausal age, and period of edentulousness. The bone mineral content measured in vivo by dual-photon scanner was significantly lower in the mandible and the forearm bones (that is, in the skeleton) of the osteoporotic group than it was in the normal group. No significant difference between the two groups was demonstrated with respect to the size of the mandibular sagittal area, measured on identical lateral cephalograms, while the sagittal maxillary area was significantly smaller in the osteoporotic group. Symptomatic osteoporosis therefore seems to be a severe risk factor for smaller residual ridge reduction off the maxillae, while this does not seem to be the case in the mandible.

Lack of effect of nasal salmon calcitonin on cell-mediated immunity.

The calcium lowering hormone, calcitonin, also affects the immune system. The effect of nasal salmon calcitonin on lymphocyte transformation tests and on serum-ionised calcium was investigated in a randomised, double-blind and placebo-controlled study including 24 healthy adult volunteers. The participants received a single dose of either 200 IU of nasal salmon calcitonin or nasal placebo in the morning and measurements were done before and 3 h after administration of the spray. Nasal salmon calcitonin exerted a significant hypocalcemic effect, but did not interfere with antigen- or mitogen-induced expansion of T-lymphocytes. It is unlikely that nasal salmon calcitonin affects cell-mediated immunity in healthy subjects.

Urinary hydroxypyridinium cross-links of collagen in rheumatoid arthritis. Relation to disease activity and effects of methylprednisolone.

Pyridinoline (Pyr) and deoxypyridinoline (Dpyr) are new markers of type I and II collagen degradation. Dpyr is a specific marker of type I collagen resorption in bone, whereas Pyr is released from type I and II collagen in bone and cartilage. We assessed the effect of six repeated iv methylprednisolone (MP) pulses or placebo at 4 week intervals in combination with DMARDs, on the excretion of Pyr and Dpyr in 86 patients with active RA. Pyr and Dpyr correlated significantly with clinical and biochemical markers of disease activity. After an initial decrease in Pyr on day 7 in the MP treated group, Pyr was significantly increased in both treatment groups at day 28. Dpyr remained unchanged after a single MP pulse in contrast to significant increases after 7 and 28 days in the placebo group. Pyr and Dpyr were significantly decreased after 24 and 52 weeks in the MP group, whereas no changes were observed in the placebo group. Pyr and Dpyr correlate with clinical and biochemical markers of disease activity in patients with active RA. Repeated MP pulses in combination with DMARDs in RA, do not seem to have a deleterious effect on bone resorption measured by Dpyr excretion, on the contrary MP pulses may even prevent an increase in bone resorption, as indicated by the decreased Dpyr observed in this group.

Quantitation of urinary hydroxypyridinium cross-links from collagen by high-performance liquid chromatography.

Pyridinoline and deoxypyridinoline are intermolecular cross-links in mature collagen in bone and cartilage. The urinary excretion of the two compounds correlates well to bone turnover. A fast, sensitive, and accurate isocratic ion-pairing reverse-phase high-performance liquid chromatography method for measurement of pyridinoline and deoxypyridinoline in urine has been established. Intra- and inter-assay precision were 5-7% and 12-14%, respectively. Recovery for pyridinoline was 97.4% and for deoxypyridinoline 94.3%. The detection limit was 0.4 pmol. Pyridinoline:creatinine and deoxypyridinoline: creatinine ratios in healthy subjects, were 38.8 nmol:mmol and 13.0 nmol:mmol, respectively. Increased values of both cross-links were observed in children, in the age group 20-29 in both sexes, and in post-menopausal women.

Bone mineral content and bone metabolism in young adults with severe periodontitis.

OBJECTIVES: To clarify in young adults with severe periodontitis (1) whether the bone mineral content (BMC) or density (BMD) in the mandible/other skeletal sites and the systemic bone metabolism differed from normal and (2) whether mandibular/forearm BMC did change during the 5 to 10-year follow-up. MATERIAL AND METHODS: 24 young otherwise normal patients with verified severe periodontitis were included, of which 20 attended the follow-up visit. Mandibular/forearm BMC was measured at both visits by dual-photon absorptiometry, supplemented with femoral neck/lumbar spine BMD measurements at follow-up visit by dual-energy X-ray absorptiometry. Serum alkaline phosphatase/ionized calcium, urinary excretion of pyridinoline/deoxy-pyridinoline were analysed at the follow-up visit. A conventional periodontal examination was performed at both visits. RESULTS: Mandibular BMC was significantly below normal mean BMC at both visits. The mandibular Z-scores were < or = -2.00 in 33.3% (8/24). BMC/BMD in the remaining sites and the values for bone markers did not differ from normal. Mandibular/forearm BMC was stable while a significant aggravation of alveolar bone loss occurred during the trial without change of probing depth. CONCLUSIONS: Severe periodontitis in young adults seems to be a local disorder associated with relatively low BMC in the jaws without systemic alterations of BMC/BMD and bone metabolism.

Assessment of different markers of bone resorption in postmenopausal osteoporotic women treated with pamidronate.

The aim of this study was to evaluate the different bone resorption markers, total pyridinoline (Pyr) and total deoxypyridinoline (Dpyr), assessed by a HPLC method, free Dpyr, assessed by a new immunoassay, and urinary excretion of hydroxyproline (OH-proline), in postmenopausal osteoporotic women during long-term treatment with pamidronate. A total of 60 postmenopausal women with previous distal forearm fracture were included in this 12-month placebo-controlled and double-blind study, where intermittent oral pamidronate, 75 or 150 mg, or placebo were given daily for 4 weeks, every 16 weeks. After 1 week a significant reduction in urinary excretion of total Dpyr was observed in the group treated with 150 mg pamidronate compared to the placebo (p < 0.01) and to the 75-mg group (p < 0.001). A maximal 50.4% decrease in total Dpyr, (p < 0.0001 compared to the placebo group, p < 0.01 compared to the 75-mg group), was observed after 3 weeks of treatment with 150 mg pamidronate, and this decrease persisted to week 52. After 4 weeks of treatment with 150 mg pamidronate the maximal decrease in free Dpyr was only 26.5%, which persisted during 12 months of treatment. Decreases in urinary excretion of total Pyr and OH-proline were less than the decreases in total Dpyr. The correlation between total Dpyr (HPLC method) and free Dpyr (Pyrilinks-D assay) at baseline was r = 0.91. Total Dpyr assessed by the HPLC method reflects the pamidronate-induced decrease in bone resorption, and the changes in this resorption marker were more pronounced than changes in free Dpyr, total Pyr and OH-proline. In this study free Dpyr analysis was less suitable for reflecting bone resorption during bisphosphonate therapy.

Serum and urinary markers of types I and III collagen turnover during short-term prednisolone treatment in healthy adults.

During recent years new sensitive serum and urinary makers have been introduced for assessment of collagen turnover. The aim of the present study was to assess whether short-term prednisolone treatment is associated with any adverse effects on serum levels of the type I collagen synthesis marker, the carboxy terminal propeptide of type I procollagen (PICP); on the type I collagen degradation marker in serum, the carboxy terminal pyridinoline cross-linked telopeptide of type I collagen (ICTP); on a serum marker of type III collagen synthesis, the aminoterminal propeptide of type III procollagen (PIIINP), or on the type I collagen degradation markers urinary pyridinoline (PYD) and deoxypyridinoline (DPD) concentrations. We studied 12 men and 8 premenopausal women aged 19-45 years (mean 31). All subjects were healthy. The design was a randomized double-blind, placebo-controlled parallel group study with a 2-day run-in, a 3-day treatment period and a 4-day run-out. During run-in and run-out no medication was given. During the treatment period the subjects took either prednisolone, 40 mg per day, or placebo. Blood and urine were collected at the last day of each period. The intergroup comparisons of run-in treatment values showed that prednisolone suppressed PICP (p < 0.001) and PIIINP (p < 0.001). PICP levels remained suppressed during run-out, whereas PIIINP returned to pretreatment levels. NO prednisolone-induced effects on ICTP or on urinary PYD or DPD were detected by the intergroup comparisons. Short-term prednisolone treatment is associated with suppressive effects on type I and III collagen turnover. Whether serum PICP is more sensitive than urinary PYD and DPD for detection of short-term suppressive effects on type I collagen turnover remains to be further evaluated.

Decreased bone mineral density in patients with pustulosis palmaris et plantaris.

BACKGROUND: Focal skeletal changes in patients with pustulosis palmaris et plantaris (PPP) are known to occur in a minority of patients. It is unknown whether these changes are unique events or whether they merely represent more progressed cases. OBJECTIVE: The study was undertaken in order to investigate possible diffuse bone changes in patients with PPP. METHODS: Bone mineral density (BMD) and biochemical markers of bone turnover were studied in 18 female patients and 18 age-matched controls. RESULTS: A significant correlation was found between lower-forearm BMD and disease duration (< 0.05). With increasing age, patients had significantly lower values than controls for both forearm and spine BMD (p < 0.005); patients who had PPP for more than 2 years had significantly reduced forearm BMD (19.8%; 95% CI: 5.6-32.8%) and spine BMD (17.4%; 95% CI: 0.9-33.8%). No significant differences were observed in biochemical markers of bone turnover, physical activity or body mass index between patients and controls. The proportion of smokers among patients was four times higher than among controls (p < 0.0005). No significant dose effect was found between number of pack-years and BMD. CONCLUSION: Although we cannot exclude that prolonged use of topical steroids under occlusion is a confounding factor, the study suggests that PPP patients have decreased BMD due to primary pathogenic events, and that osteoporosis may be an additional problem for these patients.

Collagen-derived markers of bone metabolism in osteogenesis imperfecta.

Markers of bone formation [C-terminal and N-terminal propeptides of procollagen I (PICP, PINP), osteocalcin and alkaline phosphatase] and bone resorption [C-terminal cross-linked telopeptide of collagen I (ICTP) and hydroxypyridinium cross-links, pyridinoline (Pyr) and deoxypyridinoline (Dpyr)] were measured in 78 osteogenesis imperfecta (OI) patients to investigate bone metabolism in vivo and relate marker concentrations to phenotype and in vitro collagen I defects, as shown by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). PICP and PINP were generally low, and the serum levels were lower in all children and adults with mild OI and a quantitative collagen defect than in patients with severe OI and a qualitative collagen I defect. ICTP, Pyr and Dpyr were generally normal or reduced, but elevated in severely affected adults with a qualitative collagen I defect. The in vivo findings correlated with in vitro results of collagen I SDS-PAGE. Bone turnover is reduced in OI children and mildly affected OI adults, whereas bone resorption is elevated in severely affected adults. These findings may prove helpful for diagnosis and decision-making regarding therapy in OI.

Adverse effects of inhaled budesonide (800 micrograms) on growth and collagen turnover in children with asthma: a double-blind comparison of once-daily versus twice-daily administration.

BACKGROUND: Twice-daily administration of inhaled budesonide (400 micrograms) suppresses short-term growth in children with asthma. OBJECTIVE: To compare short-term growth and markers of collagen turnover during treatment with 800 micrograms of inhaled budesonide administered once daily in the morning and 400 micrograms administered twice daily. PATIENTS: Twenty-four children with asthma aged 5.6 to 12.5 years. SETTING: An outpatient secondary referral center. METHODS: A randomized, double-blind, crossover trial with 2 treatment periods of 4 weeks was conducted, and growth was assessed with a knemometer. The carboxy terminal propeptide of type I procollagen, the amino terminal propeptide of type I procollagen (PINP), the carboxy terminal pyridinoline cross-linked telopeptide of type I collagen, the amino terminal propeptide of type III procollagen (PIIINP), and urinary pyridinoline and deoxypyridinoline were evaluated. RESULTS: Mean lower leg growth rate (P = .04), PINP (P = .03), and PIIINP (P < .01) were suppressed during twice-daily administration of budesonide, 400 micrograms. Otherwise, no statistically significant differences were detected. CONCLUSIONS: As compared with 400 micrograms of inhaled budesonide administered twice daily, 800 micrograms administered once daily in the morning has a sparing effect on short-term growth and collagen turnover.