Biomedical subjects

C Moniz

Publications and source records attributed to C Moniz.

At least 19 recordsLinked to original sources

PubMed2000

A randomized trial of nasal spray salmon calcitonin in postmenopausal women with established osteoporosis: the prevent recurrence of osteoporotic fractures study. PROOF Study Group.

PURPOSE: We conducted a 5-year, double-blind, randomized, placebo-controlled study to determine whether salmon calcitonin nasal spray reduced the risk of new vertebral fractures in postmenopausal women with osteoporosis. SUBJECTS AND METHODS: A total of 1,255 postmenopausal women with established osteoporosis were randomly assigned to receive salmon calcitonin nasal spray (100, 200, or 400 IU) or placebo daily. All participants received elemental calcium (1,000 mg) and vitamin D (400 IU) daily. Vertebral fractures were assessed with lateral radiographs of the spine. The primary efficacy endpoint was the risk of new vertebral fractures in the salmon calcitonin nasal spray 200-IU group compared with the placebo group. RESULTS: During 5 years, 1,108 participants had at least one follow-up radiograph. A total of 783 women completed 3 years of treatment, and 511 completed 5 years. The 200-IU dose of salmon calcitonin nasal spray significantly reduced the risk of new vertebral fractures by 33% compared with placebo [200 IU: 51 of 287, placebo: 70 of 270, relative risk (RR) = 0.67, 95% confidence interval (CI): 0.47- to 0.97, P = 0.03]. In the 817 women with one to five prevalent vertebral fractures at enrollment, the risk was reduced by 36% (RR = 0.64, 95% CI: 0.43- to 0.96, P = 0.03). The reductions in vertebral fractures in the 100-IU (RR = 0.85, 95% CI: 0.60- to 1.21) and the 400-IU (RR = 0.84, 95% CI: 0.59- to 1.18) groups were not significantly different from placebo. Lumbar spine bone mineral density increased significantly from baseline (1% to 1. 5%, P<0.01) in all active treatment groups. Bone turnover was inhibited, as shown by suppression of serum type-I collagen cross-linked telopeptide (C-telopeptide) by 12% in the 200-IU group (P <0.01) and by 14% in the 400-IU group (P<0.01) as compared with placebo. CONCLUSION: Salmon calcitonin nasal spray at a dose of 200 IU daily significantly reduces the risk of new vertebral fractures in postmenopausal women with osteoporosis.

Aged↗

PubMed2000

A pooled data analysis on the use of intermittent cyclical etidronate therapy for the prevention and treatment of corticosteroid induced bone loss.

OBJECTIVE: To conduct a pooled data analysis in a group of patients defined by sex, menopausal status, and underlying disease in order to examine the effect of intermittent cyclical etidronate in the prevention and treatment of corticosteroid induced osteoporosis. METHODS: We selected 5 randomized, placebo controlled studies that examined the efficacy of intermittent cyclical etidronate therapy in which the raw data were available for analysis. Three were prevention studies and 2 treatment studies. The primary outcome was the difference between treatment groups in the percentage change from baseline in lumbar spine bone density. Secondary outcomes included the difference between treatment groups in the percentage change from baseline in femoral neck and trochanter bone density, and vertebral fracture rates. RESULTS: Results are separately pooled for the prevention and treatment studies. The prevention studies had significant mean differences (95% CI) between groups in mean percentage change from baseline in lumbar spine, femoral neck, and trochanter bone density of 3.7 (2.6 to 4.7), 1.7 (0.4 to 2.9), and 2.8% (1.3 to 4.2) after one year of treatment, in favor of the etidronate group. The treatment studies displayed a mean difference between groups in mean percentage change from baseline in lumbar spine bone density of 4.8 (2.7 to 6.9) and 5.4% (2.5 to 8.4) after one and 2 years of therapy. In the prevention studies, a reduced fracture incidence was observed in the etidronate group compared with the placebo group (relative risk 0.50; CI 0.21 to 1.19). CONCLUSION: Etidronate therapy was effective in preventing bone loss in the prevention studies and in preventing or slightly increasing bone mass in the treatment studies. A fracture benefit was observed in postmenopausal women treated with etidronate in the prevention studies.

Adult↗

PubMed1999

Non-invasive assessment of bone density in primary biliary cirrhosis.

BACKGROUND/AIMS: Low bone mass is an important complication of primary biliary cirrhosis (PBC), resulting in an increased risk of fractures and reduced mobility. In the present study, we sought to determine the frequency of low bone mass in PBC, and its relationship to disease severity and non-invasive markers of bone turnover. METHODS: In 36 women with PBC, bone mineral density of the lumbar spine and hip was assessed by dual emission X-ray absorptiometry. Serum and urinary markers of bone turnover were compared with those from age- and sex-matched controls. RESULTS: Spinal osteopenia (T score, -1.5 to -2.5) was present in 15 of the 36 patients (42%), while six others (16%) had established osteoporosis (T < -2.5). Osteopenia of the femoral neck was found in 17 patients (47%), and osteoporosis in five (14%). The severity of liver disease, as determined by Mayo Clinic R score and histological stage, correlated negatively with both regional bone mineral density and total bone mineral content expressed as a ratio to lean body mass. There was a strong positive correlation between serum levels of the procollagen degradation peptides, PICP and PIIINP (r = 0.65, P < 0.001), and both peptides correlated significantly (P < 0.001) with histological stage and Mayo Clinic R score. Fasting urinary pyridinoline and deoxypyridinoline to creatinine ratios were also significantly raised. CONCLUSIONS: Low bone mass in PBC correlates positively with disease severity, and is associated with a net increase in bone resorption, as assessed by urinary collagen cross-link excretion. These markers of bone turnover may be of value in controlled clinical trials aimed at improving bone mass in PBC.

Absorptiometry, Photon↗

PubMed1998

A double blind placebo controlled study to determine the effects of intermittent cyclical etidronate on bone mineral density in patients on long-term oral corticosteroid treatment.

BACKGROUND: A double blind, placebo controlled study was undertaken to determine the effects of 104 weeks of intermittent cyclical etidronate therapy on bone mineral density (BMD) in patients undergoing long-term oral corticosteroid therapy. METHODS: Forty nine patients of mean age 59 years on long-term (> 6 months) corticosteroid treatment were randomised to receive either 400 mg/day etidronate or placebo for 14 days followed in both groups by calcium (equivalent to 97 mg elemental Ca/day) with vitamin D (400 IU) for 76 days. The cycle was repeated a total of eight times over a period of two years. Dual energy x ray absorptiometry (DEXA) measurements of the lumbar spine and hip BMD and biochemical bone marker analyses were performed at baseline and every six months. RESULTS: Twenty six patients (10 men) received cyclical etidronate and 23 (nine men) received placebo. The mean (SD) dose of corticosteroid (prednisone or equivalent) at baseline in the etidronate group was 8 (4) mg/day and in the placebo group was 7 (4) mg/day. Most of the patients (43%) suffered from asthma. Forty one patients completed the study (22 in the etidronate group and 19 in the placebo group). All had a low BMD at entry and with treatment a significant difference was observed between groups in the mean (SE) percentage change from baseline in lumbar spine BMD at week 104 of 4.5 (1.65)% (p = 0.007) with a 95% confidence interval (CI) of 1.12 to 7.87%. No clinically or statistically significant treatment differences were observed at the hip or with bone markers. The incidence of adverse events was similar in the two groups. CONCLUSIONS: The results show that intermittent cyclical etidronate therapy with calcium and vitamin D supplementation significantly increases lumbar spine BMD in patients with osteoporosis resulting from long-term treatment with corticosteroids.

Aged↗

PubMed1998

Dissociation of bone turnover in anorexia nervosa.

Biochemical markers were measured to assess bone turnover in a cross-sectional study of 43 patients with anorexia nervosa; 28 were at their first assessment (untreated) with a body mass index (BMI) (median interquartile range) of 13.3 (2) kg/m2. A second group of 15 patients undergoing treatment (treated) had a median BMI of 17.6 (2.8) kg/m2. The median, interquartile range of urinary deoxypyridinoline (DPyd), a bone resorption marker, was raised in both groups compared with an age-matched control population [DPyd = 17.8 (15.2), 17.5 (16.4) and 9.2 (4.0) nmol/mmol creatinine, respectively]. Serum type 1 collagen carboxyterminal propeptide (P1CP), a marker of bone formation, was similar to controls in the untreated patients [112 (29) and 112 (78.5) ng/ml, respectively], but was significantly raised in the treated patients [163 (219) ng/ml, P < 0.05]. A second group of 21 patients was followed prospectively, on admission and during 8 weeks of intensive inpatient care (BMI on admission and after 8 weeks was 13.0 (2) and 16.7 (3) kg/m2, respectively). The resorption marker, serum type 1 collagen carboxyterminal telopeptide (1CTP) was raised on admission and remained high during treatment. P1CP and osteocalcin levels were similar to control levels on admission but increased with treatment, and after 8 weeks were 40% and 63% higher respectively than on admission. These findings suggest that in untreated anorexia nervosa there was uncoupling of bone turnover as bone resorption markers were raised without a concomitant increase in bone formation markers. As the condition was treated and patients gained weight, the formation markers also increased, leading to a more balanced, although higher, bone turnover.

Alkaline Phosphatase↗

PubMed1997

Molecular cloning of human GATA-6 DNA binding protein: high levels of expression in heart and gut.

Human GATA-6 has been cloned from foetal heart by a combination of PCR-based methods and cDNA library screening. The 3.8 kbp cDNA has a coding sequence of 1347 bp the 449 aa protein is virtually identical in the two zinc-finger binding domains to other human GATA sequences, but varies considerably in the amino and carboxy terminal regions. The sequence shows greatest similarity to GATA-6-like sequences from rat, mouse, chicken and Xenopus. Northern analysis and in situ hybridisation show that GATA-6 is expressed at high levels in human adult and foetal heart as well as in gut derivatives. It is postulated that GATA-6, in concert with GATA-4, plays a crucial role in the regulation of cardiac differentiation.

Amino Acid Sequence↗

PubMed1997

Measurement of markers of osteoclast and osteoblast activity in patients with acute and chronic diabetic Charcot neuroarthropathy.

Excess osteoclast activity is believed to be responsible for the early bone changes associated with Charcot neuroarthropathy in diabetes mellitus. Markers of osteoclast and osteoblast activity were measured in four groups of patients: 16 with an acute Charcot foot, 16 with a chronic Charcot foot, 10 diabetic controls, and 10 non-diabetic controls. Serum carboxyterminal telopeptide of type 1 collagen (1CTP), a marker of osteoclastic bone resorption, was significantly raised in the dorsal venous arch of the acute Charcot foot, 6.1 +/- 1.5 microg l(-1) (mean +/- SD) compared with the chronic Charcot foot 4.1 +/- 1.4, diabetic controls 3.3 +/- 1.4, and non-diabetic controls 2.8 +/- 1.4, p < 0.0001. This local increase in 1CTP was also reflected systemically in a study subgroup of 6 patients with acute Charcot neuroarthropathy, in whom peripheral antecubital vein 1CTP was 9.2 +/- 2.6 compared with 9.0 +/- 3.1 in the foot. In 6 chronic Charcot neuroarthropathy patients, foot (3.8 +/- 1.3) and systemic (4.0 +/- 1.5) 1CTP values were similar. Serum procollagen carboxyterminal propeptide (P1CP), an indicator of osteoblastic bone formation, was not significantly different between the feet of patients with acute Charcot neuroarthropathy 112 +/- 1.5 microg l(-1), patients with chronic Charcot neuroarthropathy 109 +/- 1.5 microg l(-1), diabetic controls 93.5 +/- 2.3 microg l(-1), and non-diabetic controls 90.1 +/- 1.5 microg l(-1). These results suggest that the acute Charcot foot demonstrates excess osteoclastic activity without concomitant increase in osteoblastic function. This may be important in its pathogenesis.

Acute Disease↗

PubMed1997

Effects of inflammation and treatment on bone turnover and bone mass in polymyalgia rheumatica.

OBJECTIVE: Polymyalgia rheumatica (PMR) has an abrupt onset of inflammatory symptoms, making it a useful model for studying the effects of inflammation in bone. PMR requires corticosteroid treatment, which may itself have a detrimental effect on bone. This study used serially measured biochemical markers of bone turnover and bone density to address the relative contributions of systemic inflammation and corticosteroid therapy to bone loss. METHODS: Fifty untreated patients with PMR were randomized to receive oral prednisolone or intramuscular methylprednisolone. Biochemical bone markers (pyridinoline [PYR], deoxypyridinoline [DPYR], procollagen type I carboxy-terminal peptide [PICP]) and bone mineral density (BMD) were measured at baseline and at 6, 12, and 24 months. RESULTS: The median disease duration at presentation was 12 weeks (range 5-32 weeks). Levels of urinary crosslinks were increased in patients with untreated PMR compared with controls (PYR 74.9 +/- 30.0 nmoles/mmole creatinine, DPYR 14.6 +/- 6.4 nmoles/mmole creatinine [mean +/- SD]; P = 0.0001); the PICP level was normal (115.0 +/- 39.0 microg/liter). With treatment, the crosslinks levels fell and PICP levels rose within 6 months (P = 0.01). Bone resorption (PYR) correlated with untreated disease activity (erythrocyte sedimentation rate [ESR]) (r = 0.5, P = 0.003) and with interleukin-6 levels (r = 0.48, P = 0.05). There was a significant reduction in BMD of both the hip and the spine after 12 months of treatment (P = 0.0002), with no difference between treatment groups. As the steroid dosage was reduced, bone mass improved. Initial ESR influenced the percent change in BMD at 1 year (r = 0.35, P = 0.05), while cumulative steroid dose, mean ESR, and type of steroid used did not. CONCLUSION: Inflammation in PMR increases bone resorption and appears to have a more detrimental effect on bone than does low-dose corticosteroid. If corticosteroids can be tapered and discontinued, bone loss in PMR can be a transient phenomenon.

Adrenal Cortex Hormones↗

PubMed1997

Effect of calcium intake and physical activity level on bone mass and turnover in healthy, white, postmenopausal women.

Calcium intake and physical activity level (PAL) were assessed by questionnaire in 124 healthy women aged 52-62 y to determine the effect of calcium intake and PAL on bone mass and turnover. Four groups were identified according to their different reported calcium intakes and PALs. Bone mineral density (BMD) at the spine, hip, and left os calcis was measured together with total bone mineral content (TBMC) with dual-energy X-ray absorptiometry. Bone formation and resorption biochemical markers were measured in fasting samples of blood and urine. Women with the highest calcium intakes and PALs had the highest BMD at all sites compared with those with the lowest calcium intakes and PALs (P < 0.001). Calcium intake and PAL were positively correlated with BMD at all sites. Bone turnover markers did not explain the variation in bone mass between groups. In stepwise-multiple-regression analysis only calcium intake, physical activity, age, or weight remained as independent predictors of BMD and TBMC. When subjects were divided by past PALs, calcium intake and PAL were second to age and weight in their influence on spinal and hip BMD, but remained influential on the os calcis and whole body. We conclude that current high calcium intakes and PALs influence BMD at the os calcis and TBMC and protect bone mass in women 5-12 y postmenopausal at all measured sites, including the spine and hip. This finding does not exclude the possibility of past influences of calcium and activity on bone mass.

Biomarkers↗

PubMed1997

Reduced bone density in patients with inflammatory bowel disease.

BACKGROUND: Reduced bone mineral density in patients with inflammatory bowel disease is thought to be due to disturbances in calcium homeostasis or the effects of corticosteroid treatment. AIMS: To assess the prevalence and mechanism of reduced bone mineral density in 79 patients with inflammatory bowel disease (44 with Crohn's disease, 35 with ulcerative colitis) who did not have significant risk factors for low bone densities. METHODS: Dual x ray absorptiometry was used to measure bone mineral density and serum and urinary markers of osteoblast (alkaline phosphatase, procollagen 1 carboxy terminal peptide and osteocalcin) and osteoclast (pyridinoline, deoxypyridinoline, and type 1 collagen carboxy terminal peptide) activities to assess bone turnover. RESULTS: There was a high prevalence of low bone mineral density (prevalence of T scores < -1.0 from 51%-77%; T scores < -2.5 (osteoporosis) from 17%-28%) with hips being more often affected than vertebrae (p < 0.001). Reduced bone mineral density did not relate to concurrent or past corticosteroid intake, or type, site, or severity of disease. Whereas calcium homeostasis was normal, bone markers showed increased bone resorption without a compensatory increase in bone formation. CONCLUSIONS: The greater prevalence of reduced hip bone mineral density, as opposed to vertebral, mineral density and the pattern of a selective increase in bone resorption contrasts with that found in other known causes of metabolic bone disease.

Absorptiometry, Photon↗

PubMed1996

A comparison of the effects of alfacalcidol treatment and vitamin D2 supplementation on calcium absorption in elderly women with vertebral fractures.

Although vitamin D supplementation in the frail elderly improves calcium absorption, suppresses parathyroid hormone, decreases bone loss and reduces the risk of fractures, such treatment may be ineffective in patients with vertebral osteoporosis, because of impaired vitamin D metabolism or resistance to the action of vitamin D metabolites on the bowel. We have therefore performed a randomized, single masked study comparing the effects of alfacalcidol treatment (0.25 micrograms twice daily) and vitamin D2 supplementation (500-1000 units daily) on calcium absorption and bone turnover in 46 elderly women (median age 69 years, range 64-79 years) with radiological evidence of vertebral fractures. Serum 25-hydroxyvitamin D increased significantly after 3 and 6 months of treatment with vitamin D2 (p < 0.001), but was unchanged in the group receiving alfacalcidol. Serum 1,25-dihydroxyvitamin D did not change significantly in either group over the study period. Fractional 45Ca absorption increased after 3 months of treatment with alfacalcidol (p < 0.05), but was unchanged with vitamin D2. There was also a reduction in plasma intact parathyroid hormone and serum alkaline phosphatase after 6 months of treatment with alfacalcidol (p < 0.05) which was not seen in the group receiving vitamin D2. Our study shows that vitamin D2 supplementation is ineffective in stimulating calcium absorption in elderly women with vertebral osteoporosis. By increasing calcium absorption in such patients, alfacalcidol may prove more effective than vitamin D in the management of vertebral osteoporosis.

Absorption↗

PubMed1996

Colitis causes bone loss in rats through suppression of bone formation.

BACKGROUND & AIMS: Idiopathic inflammatory bowel disease (IBD) is associated with bone loss in more than 30% of cases. Nevertheless, the pathogenesis of the bone loss is uncertain. The aim of this study was to investigate the bone loss and underlying mechanisms using an animal model of IBD. METHODS: Severe colitis was induced by intrarectal administration of a hapten, 2,4,6-trinitrobenzenesulfonic acid (TNBS). Severity of IBD was graded macroscopically and histologically. Bone histomorphometry was performed on cancellous bone of the tibiae. RESULTS: A florid transmural colitis was observed 3 weeks after administration of TNBS. In these animals, there was considerable cancellous bone loss of 33% compared with age-matched, pair-fed control animals. This was associated with a marked suppression of the cancellous bone formation rate to < 30% of that in control animals. Thereafter, bone formation rate increased in parallel with healing of colitis. Twelve weeks after TNBS administration, the persistent increase in bone formation rate was associated with return of bone volume to control levels. CONCLUSIONS: The data suggest that bone loss can occur rapidly in colitis and is associated with suppression of bone formation. This study also shows that the bone loss that occurs during TNBS-induced colitis is reversible.

Animals↗

PubMed1994

Carboxyterminal propeptide of type I procollagen in osteomalacia.

Carboxyterminal propeptide of type I procollagen (PICP) was measured in sera from 25 patients with osteomalacia due to privational vitamin D deficiency. The mean value of serum PICP was significantly raised in patients with osteomalacia compared with 40 normal subjects (mean +/- SD, 161 +/- 82 ng/ml and 113 +/- 31 ng/ml, respectively; P = 0.01). The raised serum PICP reflected the accelerated bone turnover in this condition as did the elevated serum total alkaline phosphatase (ALP), but the variation in values of serum PICP noted in individual patients may reflect the different stages of osteomalacia. The normalization of serum PICP and ALP, indicating a healing process of the bone disorder, needed longer time of vitamin D and calcium therapy. In contrast, adjusted serum calcium and inorganic phosphate (IP) responded and normalized rapidly. Serum PICP and total ALP appeared to behave differently in the disease and in its response to vitamin D therapy suggesting that these two markers may represent different functions of osteoblasts in osteomalacia.

Adult↗

PubMed1994

Alcohol and bone.

It is well known that the prolonged use of excess alcohol causes a multiplicity of abnormal clinical, biochemical and electrophysiological changes that are associated with diseases of the liver, neuromuscular system, heart and brain. It is less well appreciated that the long-term use of excess alcohol also effect bone and may play an important role in the causation of extensive bone loss, and osteoporosis.

Aged↗

PubMed1994

The role of parathyroid hormone-related protein in calcium homeostasis in the fetal pig.

The concentrations of plasma parathyroid hormone-like bioactivity and parathyroid hormone-related protein (1-86) (PTHrP) immunoreactivity were both higher in fetal pigs than in their mothers during the last 3 weeks of gestation. Both activities changed inversely with alterations in the plasma ionized calcium concentration. The data suggest that PTHrP may have a role in calcium homeostasis in the fetal pig, similar to its postulated role in sheep in the stimulation of calcium transport across the placenta.

Animals↗

PubMed1994

Systemic bone changes accompanying early rheumatoid arthritis in patients treated with nonsteroidal antiinflammatory drugs alone.

Seventeen patients suffering from early rheumatoid disease (mean duration, 3.5 years) and treated with nonsteroidal antiinflammatory drugs alone had evidence of systemic bone changes. Transiliac bone biopsies, compared with age and gender-matched controls, demonstrated reduced bone volume and increased eroded surface. In addition, the metacarpal indices were reduced in the rheumatoid patients and correlated with the iliac crest bone volume. These changes, found distal from sites of synovitis, suggest that in this group of rheumatoid patients there were systemic changes of bone metabolism. No biochemical abnormalities of calcium homeostasis were found. Collectively, present observations may be a reflection of the rheumatoid disease process itself.

Adult↗

PubMed1993

Parathyroid hormone related peptide gene expression in human fetal and adult heart.

OBJECTIVE: The aim was to investigate the expression of parathyroid hormone related peptide (PTHrP) gene in the human fetal and adult heart. METHODS: Molecular biological techniques were employed as well as immunocytochemistry and western blot analysis using rabbit polyclonal anti-PTHrP(1-34) and anti-PTHrP (56-86) on normal human fetal and adult heart tissues. Northern blot analysis of both normal human fetal and adult heart total RNA, using a human full length cDNA probe, and polymerase chain reaction analysis of normal human fetal and adult heart cDNAs with exon specific oligonucleotides were carried out. RESULTS: Positive staining was detected with both anti-PTHrP(1-34) and anti-PTHrP(56-86) in fetal heart at 12 weeks of gestation. In both fetal and adult hearts, multiple putative PTHrP proteins were observed with apparent molecular mass of 14-125 kDa. Multiple hybridising PTHrP mRNA isoforms (1.4, 2.1, 3.2, and 4.5 kb) were detected in both fetal and adult heart total RNAs. The fetal and adult heart cDNAs amplified from the cDNA libraries showed the presence of the 5' non-coding exon II and coding exons III-IV but not the 5' non-coding exon Ic. CONCLUSIONS: PTHrP is expressed in normal human fetal and adult hearts suggesting that it has a function as an endogenous modulator of the cardiovascular system.

Adult↗

PubMed1993

Biochemical markers of bone turnover in women with surgically treated carcinoma of the breast.

Biochemical markers of bone turnover were measured in fasting urine and blood samples obtained from 38 postmenopausal women with previous surgical treatment of breast cancer combined with adjuvant chemotherapy, tamoxifen, or placebo. Significantly elevated urinary pyridinoline as nmol mmol-1 creatinine (47.5 and 42.5 in tamoxifen and placebo treated patients compared with 26.3 in normal controls, both P < 0.001) and deoxypyridinoline (11.9 and 10.5 compared with 6.3, P < 0.001 and P = 0.002 respectively) were found with unchanged urinary hydroxyproline, serum alkaline phosphatase and procollagen I carboxyterminal peptide (PICP). These findings suggest enhanced bone resorption resulting from the humoral osteoclast activating effect of the previous breast cancer or underlying carcinoma recurrence. Alternatively the raised pyridinium excretion might indicate an altered crosslinking composition of bone collagen. No specific effect on bone metabolism was found with tamoxifen treatment as all measured parameters were similar in both tamoxifen ex-users and non-users. This confirmed the safety of tamoxifen therapy with respect to bone.

Aged↗