Search

Male osteoporosis represents an important, although long underestimated, public health problem. Both in men and in women aging is accompanied by continuous bone loss and by an exponential increase in [...]

Osteoarthritis‐related changes in joint space measurements over time are small and sensitive to measurement error. The Reliable Change Index (RCI) determines whether the magnitude of change observed in an individual can be attributed to true change. This study aimed to examine the RCIas a novel approach to estimating osteoarthritis progression. Data were from 167 men and 392 women with knee osteoarthritis (diagnosed using the American College of Rheumatology criteria) randomized to the placebo arm of the 3‐year Strontium Ranelate Efficacy in Knee Osteoarthritis trial (SEKOIA) and assessed annually. The RCIwas used to determine whether the magnitude of change in joint space width (JSW) on radiographs between study years was likely to be true or due to measurement error. Between consecutive years, 57–69% of participants had an apparent decrease (change <0) in JSW, while 31–43% of participants had annual changes indicating improvement in JSW. The RCIidentified JSWdecreases in only 6.0% of patients between baseline and year 1, and in 4.5% of patients between the remaining study years. The apparent increases in JSWwere almost eliminated between baseline and year 1, and between years 1 and 2 only 1.3% of patients had a significant increase, dropping to 0.9% between years 2 and 3. The RCIprovides a method to identify change in JSW, removing many apparent changes that are likely to be due to measurement error. This method appears to be useful for assessing change in JSWfrom radiographs in clinical and research settings.

Objectives. To analyse the effect of a dose increase in patients with severe rheumatoid arthritis (RA) with insufficient clinical response to 3 mg/kg infliximab every 8 weeks.Methods. Patients suffering from active refractory RA despite methotrexate, were treated with i.v. infusions of infliximab (3 mg/kg) on week 0, 2, 6 and every 8 weeks thereafter. Based on the clinical judgement at week 22, patients received a dose increase of 100 mg from week 30 on. The American College of Rheumatology (ACR) core set for disease activity measures was regularly assessed.Results. Five hundred and eleven RA patients were included. At week 22, 61.4, 34 and 14.1% of all patients met ACR 20, ACR 50 and ACR 70 criteria, respectively, and 6.1% of patients were in remission. A low swollen joint count at baseline was correlated with improvement at week 22 for ACR 20 (P<0.06), ACR 50 (P<0.06) and ACR 70 (P<0.005). The change in HAQ score between weeks 0 and 22 was predictive for response at week 54 (P<0.01). The dose of infliximab was increased by 100 mg in 22% of the patients. Most baseline values of patients requiring dose increase were higher (P ≤ 0.001) than the baseline values of the remaining patients. Increasing the dose of infliximab by one vial from week 30 on could circumvent the partial loss of response in these patients.Conclusion. Infliximab use in this large out-patient cohort resulted in a significant clinical improvement. A subgroup that partially lost response during the first 22 weeks could regain response by adding 100 mg of infliximab to the subsequent doses. Due to the current study design, however, a regression to the mean like effect could not be ruled out.

The aim of this study was to compare the action of two regimens of intravenous (iv) pamidronate in the primary prevention of glucocorticoid‐induced osteoporosis (GC‐OP). The primary purpose of the study was to determine whether any differences in bone mineral density (BMD) appeared after 1 year. A secondary endpoint aimed at assessing the remodeling parameters in order to better understand the mechanisms of action of the various regimens. Thirty‐two patients, who required first‐time, long‐term glucocorticoid therapy at a daily dose of at least 10 mg of prednisolone, were studied. Simultaneously with the initiation of their glucocorticoid treatment, patients also were randomly allocated to receive a single iv infusion of 90 mg of pamidronate at the start (group A); a first infusion of 90 mg of pamidronate followed, subsequently, by an iv infusion of 30 mg pamidronate every 3 months (group B); and a daily 800‐mg elemental calcium supplement given as calcium carbonate (group C), which also was taken by patients in groups A and B. Patients were matched for starting glucocorticoid doses, sex, menopausal status, and hormonal replacement therapy. Lumbar spine and hip (total and subregions) BMDs were measured at the outset and repeated at 6‐month intervals by dual‐energy X‐ray absorptiometry (DXA; Hologic QDR‐2000). Bone turnover was assessed by measurement of total and bone‐specific serum alkaline phosphatase activity (B‐ALP), serum osteocalcin (OC), and serum C‐telopeptide cross‐links of type I collagen (CTX). After 1 year, the mean BMD changes for groups A, B, and C were, respectively, 1.7, 2.3, and −4.6% at the lumbar spine; 1.2, 1.2, and −3.1% at the femoral neck; 1.0, 2.6, and −2.2% for the total hip region. No difference was observed between pamidronate regimens but a highly significant difference was observed between both pamidronate regimens and the control group at the lumbar spine (p< 0.001), at the femoral neck (p< 0.01), and for the total hip (p< 0.05). A significant decrease of serum C‐telopeptide was observed, after 3 months, in groups A and B (p= 0.029), but a sustained decrease of bone resorption over time was observed only in group B. As far as BMD evolution over 1 year was concerned, iv pamidronate, given either as a single infusion or once every 3 months, effectively achieved primary prevention of GC‐OP.

Objective. To evaluate whether bone loss occurs over time in pre‐menopausal systemic lupus erythematosus (SLE) patients.Methods. We performed a longitudinal bone mineral density (BMD) analysis in a group of 35 pre‐menopausal female SLE patients. Lumbar spine and hip (total and sub‐regions) BMDs were measured twice 21 ± 11 (mean ± s.d.) months apart by dual‐energy X‐ray absorptiometry.Results. In the whole cohort of SLE patients, significant bone loss was observed at the lumbar spine (−1.22%/yr) but not at the total hip. Further analyses indicated that lumbar spine bone loss (−2.12%/yr) occurred exclusively in the subgroup of patients who had taken a mean prednisolone daily dose >7.5 mg between the two BMD measurements. Moreover, bone loss was more important in patients who had previously received a cumulative prednisolone dose ≤5 g by the time of their first BMD evaluation.Conclusions. These results, by demonstrating a loss of lumbar spine bone over time in pre‐menopausal SLE patients given glucocorticoid (GC) therapy, strongly support the use of preventive treatment to minimize GC‐induced osteoporosis in pre‐menopausal female SLE patients given prednisolone daily doses >7.5 mg.

Objective. To evaluate whether bone loss occurs over time in pre-menopausal systemic lupus erythematosus (SLE) patients.
Methods. We performed a longitudinal bone mineral density (BMD) analysis in a group of 35 pre-menopausal female SLE patients. Lumbar spine and hip (total and sub-regions) BMDs were measured twice 21 ± 11 (mean ± s.d.) months apart by dual-energy X-ray absorptiometry.
Results. In the whole cohort of SLE patients, significant bone loss was observed at the lumbar spine (-1.22%/yr) but not at the total hip. Further analyses indicated that lumbar spine bone loss (-2.12%/yr) occurred exclusively in the subgroup of patients who had taken a mean prednisolone daily dose >7.5 mg between the two BMD measurements. Moreover, bone loss was more important in patients who had previously received a cumulative prednisolone dose ≤5 g by the time of their first BMD evaluation.
Conclusions. These results, by demonstrating a loss of lumbar spine bone over time in pre-menopausal SLE patients given glucocorticoid (GC) therapy, strongly support the use of preventive treatment to minimize GC-induced osteoporosis in pre-menopausal female SLE patients given prednisolone daily doses >7.5 mg.

To study the changes in hematopoietic marrow in patients given glucocorticoid (steroid) therapy. In a cross-sectional study, high-resolution T1-weighted magnetic resonance imaging (MRI) images of the proximal femur were obtained in an unselected series of 29 premenopausal female patients with systemic lupus erythematosus (SLE) and in a series of 29 age-matched healthy female subjects. In a longitudinal analysis, 2 MRI studies were performed 19 months apart in 11 patients with SLE (including 9 patients from the cross-sectional study who were evaluated before treatment) and in 7 patients with rheumatoid arthritis (RA). The percentage of fat marrow and the index of marrow conversion (IMC) were derived from the MRI images to estimate the degree of transformation of hematopoietic into fatty marrow in the area of the femoral neck. Values observed in the cross-sectional study and their changes over time were correlated with treatment data. The cross-sectional study performed in SLE patients indicated that their mean (±SD) percentage of fat marrow (48 ± 36%) and IMC (82 ± 12) were significantly more elevated than those in the healthy control subjects (18 ± 16% and 75 ± 6, respectively) (P &lt; 0.01). The magnitude of fat conversion correlated positively with the mean daily dose of oral prednisolone, and was higher in patients with ischemic bone lesions. The longitudinal study performed in SLE and RA patients revealed that IMC changes over time correlated positively with daily prednisolone intake (r = 0.71; P = 0.001), fat conversion occurring exclusively in patients receiving a mean prednisolone dose ≤7.5 mg/day. MRI indicates that fat conversion occurs in the proximal femur of steroid-treated patients. The magnitude of fat conversion correlates with steroid intake and is higher in patients with ischemic bone lesions.

Abstract:: We addressed the clinical significance of antiproteinase 3 (anti-PR3) antibody (Ab) positivity by reviewing the files of 79 patients whose serum contained antineutrophil cytoplasmic antibodies with a cytoplasmic staining pattern (cANCA) and had been tested for anti-PR3 reactivity. Vasculitis was present in most (22/35) cANCA+ PR3+ patients but in only a few (5/44) cANCA+ PR3+ patients, thereby suggesting that anti-PR3 Ab positivity in cANCA+ patients is more indicative of vasculitis than cANCA positivity alone. Noteworthy, one-third of cANCA+ PR3+ patients – those with anti-PR3 Ab titres lower than 100 U/ml – did not suffer from vasculitis. Anti-PR3 reactivity in vasculitis patients was only weakly associated with Wegener’s granulomatosis (WG), as nine out of 22 cANCA+ PR3+ vasculitis patients (41%) did not fulfil the ACR classification criteria for WG. There was no correlation between anti-PR3 Ab titres and disease activity at diagnosis. However, titres measured when patients were in remission were much lower than initial values. Taken together, our results indicate that anti-PR3 Ab positivity should be interpreted in its clinical context.

Summary We report a case of non-Hodgkin lymphoma presenting as a painless mass of the quadriceps femoris muscle that was detected by a somatostatin analogue (octreotide) scintigraphy. We review the few reported cases of primary muscular lymphoma and discuss the potential value of octreotide imaging as a new diagnostic tool.

Summary A woman suffering from primary Sjögren 's syndrome developed sensitive neuropathy. The disease was further complicated by follicular lymphoma, an unusual albeit already described complication of Sjögren 's disease. The clinical data suggest that mononuclear infiltration of the dorsal root ganglions could be at the origin of a sensitive neuropathy, inducing an axonal degeneration of the nerves.

We report two patients with non-Hodgkin's lymphoma in whom hypercalcemia and elevated 1,25 dihydroxyvitamin D (1,25-(OH)2D3) levels developed in the absence of any lytic bone lesions. Hypercalcemia responded only transiently to glucocorticoids which were ill tolerated. Intravenous APD administration was needed to circumvene hypercalcemia. Humoral hypercalcemia of malignancy is discussed. Our cases confirm that hypercalcemia associated with elevated 1,25-(OH)2D3 may occur in malignant lymphoma.

The authors report a case of Paget's disease of bone and ocular neuromyotonia (ONM) in a 72-year-old woman. As far as we are aware, this association has never been previously described. The patient had an acquired left third cranial nerve palsy with oculomotor synkinesis and a left sixth cranial nerve palsy. Subjectively, she complained of recurring episodes of transient horizontal and vertical diplopia, lasting for about 30-40 sec and accompanied with discomfort in the left eye (LE). During those episodes, which occurred spontaneously or after sustained eccentric gaze, the LE became more esotropic with increasing restriction of abduction or hypotropic with increasing restriction of elevation. Electromyography (EMG) of the left medial rectus detected repetitive bursts of motor unit potentials with aspect of 'multiplets'. The oculomotor findings and the neurophysiological data evoked the diagnosis of ocular neuromyotonia which was subsequently confirmed by the effective response to carbamazepine. The patient had no history of radiation therapy, a frequent association of ONM. Cerebral and orbital CT scan showed a severe remodelling of the base of the skull. We suggest that cranial nerve palsies as clinically present in this patient, even if not neuroradiologically demonstrable, may result from bone thickening, especially the sphenoid and petrous bones. It is well-established that bone remodelling in Paget's disease may induce a local vascular 'steal phenomenon' which is known to cause neurological symptoms. Both mechanisms may be responsible for ONM.

Summary Sodium Fluoride (NaF) is the only medication so far clinically available with a bone formation stimulating property, through its peculiar mitogenic dose-dependent action on the osteoblast cell line. Bone strength is commensurate to bone mass, and in a condition with fragility fractures, like osteoporosis, it seems logical to restore bone mass without weakening bone strength. However, as with any active drug, NaF therapy requires adhesion to elementary rules if drawbacks are to be prevented. A first mandatory rule is not to prescribe NaF without calcium supplementation, if bone loss at the appendicular skeleton is to be avoided; to prevent this, the availability of monofluorophosphate (MEP), containing the fluoride and calcium salts in the same preparation has enhanced the compliance to calcium supplementation. A second rule is not to give supraphysiological doses of vitamin D, for the same reason. Third, if one wants to avoid a calcium shift from cortical to trabecular bone and osteomalacia, one should use small doses of NaF, of the order of 50 mg/day. With this in mind, the bioavailability of the drug has to be taken into account, particularly its gastrointestinal abosorption which is dramatically enhanced if a plain non entericoated (EC) capsule is used, as compared to that of an EC tablet with the same face value. Too much NaF is deleterious to bone, a fact known for years. Already in 1972, it was noted that in all patients receiving 60 mg or more of NEC NaF, daily, morphologically abnormal bone developed and which appeared irregular and contained areas of incompletely mineralized bone. The bone was histologically and microradiographically normal in patients receiving 45 mg or less of NEC NaF/day. Fourth, NaF therapy is contraindicated in renal insufficiency owing to an enhanced retention in the skeleton. NaF is, however, by no means the ideal medication, because its therapeutic window is narrow. It has many bothersome drawbacks, and notably it is irritating for the gastric mucosa, a hazard which may be partly circumvented by the use of an Ec or slow release tablet. Furthermore, peripheral stress fractures may occur, and, in our experience, they were seen in 17% of patients, almost exclusively in females with a low lumbar BMD. Their occurrence should be curtailed by not allowing an increase in alkaline phosphatase activity of more than 50%. This is a relatively benign complication, because no stress fracture degenerated into a complete fracture. In all cases, the stress fractures healed after a transitory drug discontinuation. If there is some concern about cortical bone, NaF therapy may be associated with an antiresorber like estrogens which will prevent any further bone loss, and does not impair the response to NaF. NaF therapy should be reserved for patients suffering chiefly from trabecular osteoporosis and shoud be avoided in senile osteoporosis, because of a frequently imparied renal function. Currently, we would recommend in clinical practice a daily dose of 50 mg EC-NaF or 150 mg Ca-MFP as the therapy of involutional osteoporosis in women, reserving the dose of 75 mg EC-NaF or 200 mg MFP for males or female patients resistant to lower dose. The therapy should be maintained for 2 to 3 years, or more, according to the bone response, taking into account that patients with the vertebral crush fracture syndrome have lost on average 30%, as compared to the young adult mean.

The authors report the observation of an alcoholic patient admitted for tetanic manifestations, in whom severe hypocalcaemia associated with hyperphosphatemia were suggestive of hypoparathyroidism. Administration of magnesium supplementation alone improved the clinical features and led to the correction of the calcium abnormalities. The mechanisms of hypomagnesemia in alcohol intoxication are reviewed as well as the links with hypocalcaemia.

The case of a 49-year-old woman suffering from generalized skeletal pain and multiple fractures accompanied by severe hypophosphataemia and low urinary phosphorus excretion is reported. She had been taking large amounts of antacids containing aluminum hydroxide for many years. A diagnosis of antacid-induced osteomalacia was made. It was confirmed by biological work-up, radiographs and bone biopsy. A dramatic biological, osteodensitometric, and clinical improvement was achieved by withdrawal of antacids and phosphorus administration. The literature concerning this unusual condition has been reviewed.

Summary A 43-year-old man suffered from migrating then additive arthralgias associated with macroscopic and microscopic cutaneous lesions compatible at first sight with reticular erythematous mucinosis. After nine months, the cutaneous picture evolved into a papular mucinosis. The patient developed ”multiple frozen joints” with heterotopic bony deposits around the hips. To our knowledge, such articular problems have not yet been described in this condition. Severe systemic complications prompted the authors to treat the patient with plasma exchange and melphalan.

Summary: Twenty-five cases of hemochromatosis established on histological grounds were reviewed in order to study their articular complaints. Symptoms relating to articular damage were the first signs of the disease in about one quarter of the cases. More than half of the patients (n=14) exhibited inflammatory arthritis, usually of the hands and knees. The arthritis was chronic in all the patients. Acute arthritis of the joints of the hands and feet appeared in the course of the disease in two patients. Chondrocalcinosis was present in 20% of cases with X-rays of joints (n=20). The classical subchondral arthropathy was observed in the metacarpophalangeal joints in 35% of the patients. In two patients chondrocalcinosis and subchondral arthropathy were both present. These data are compared with those of 66 patients suffering from primary hyperparathyroidism and of 229 controls with rheumatic complaints. The severity of the arthropathy in hemochromatosis is stressed.

Summary Subcutaneous and periarticular dystrophic calcifications are well known to be associated with progressive systemic sclerosis (PSS). On the other hand, calcifications inside the joints are very rarely reported. We report a new case of this unusual complication of PSS. The observation of the complete radiological follow-up led us to propose a mechanical rather than a purely inflammatory pathogenetic mechanism of this complication.

We determined prospectively the prevalence of avascular osteonecrosis (AON) by magnetic resonance imaging (MRI) of both lower limbs in a group of 40 systemic lupus erythematosus (SLE) patients, and correlated the results with their serum antiphospholipid antibody (APL Ab) status and their glucocorticoid (GC) intake. APL Ab were detected by anticardiolipin ELISA and by lupus anticoagulant assays. Cumulated prednisolone doses were computed by chart review. The prevalence of AON was 37.5%, with most patients being asymptomatic despite involvement of multiple sites. The number of epiphyseal, metaphyseal and diaphyseal AON sites per patient did not differ between APL Ab-positive and APL Ab-negative patients nor between patients with high and low APL Ab titres. By contrast, a striking correlation was found between the prevalence and severity of AON and GC therapy. In conclusion, this prospective MRI study indicates that the prevalence of AON in SLE patients correlates strongly with GC therapy, but not with APL Ab status.

We reviewed the side-effects of intravenous (IV) cyclophosphamide (CPM) pulse therapy in a group of 75 patients suffering from various autoimmune disorders (mostly systemic lupus erythematosus and vasculitis) who received a total of 451 IV CPM pulses, given on a monthly basis (mean ± s.d. CPM dose perpulse: 764 ± 217 mg; mean ± s.d. follow-up period: 26.7 ± 22.1 mon). Infection was the most common side-effect (30 episodes in 21 patients; 28% of the patients) but rarely required in-patient treatment (8 episodes in 7 patients; 9% of the patients). No relationship could be found between the occurrence of infection and the dose of CPM or of glucocorticoids. Other side-effects were rare. Only one patient suffered from neutropenia. Haemorragic cystitis was never observed nor did premature ovarian failure in the 25 female patients at risk. Four patients developed neoplasia and three died suddenly a few days after receiving a CPM pulse but the causal relationship between CPM therapy and these poor outcomes is speculative. Taken together, our data confirm in a large group of patients that IV CPM pulse therapy is relatively safe. In particular, the rate of severe infection requiring in-patient treatment is rare (1.8% of 451 pulses).

The value of a new computerized radiogrammetric method of assessment of the second metacarpal has been evaluated, and its results have been compared with those of single (SPA) and dual photon absorptiometry measurements (forearm and spine) in 74 and 79 postmenopausal women, respectively. Standard hand X-rays were digitized by a video-camera connected to a microcomputer. The combined cortical thickness (CCT) was automatically calculated in a zone of 10 mm around the midpart of the second metacarpal. The intra- and interobserver coefficients of variation were close to 1%. The correlation between CCT and SPA of the proximal and midforearm (with a significant amount of cortical bone) was satisfactory (r=0.62 and 0.50, respectively; P<0.001). The correlation between CCT and osteodensitometry of sites comprising more trabecular bone were not so good (0.50 for lumbar and 0.44 for distal forearm bone mineral density, respectively), but still significant (P<0.001). Radiogrammetry proved unaffected by a change of X-ray apparatus, as measurements of 48 metacarpals radiographed by two different kinds of X-ray apparatus were not significantly different. Radiogrammetry is by no means the best method to evaluate bone mass. Its automation did not improve the correlation with osteodensitometric values. Radiogrammetry is still of interest in mass screening, particularly when other more expensive techniques such as osteodensitometric methods of bone mass measurement are not readily available. Its automation makes it simpler, faster, and more precise, rendering its use easier on a larger scale.

A 12-year-old female suffering fromosteogenesis imperfecta (OI) was treated with 3-amino-1-hydroxypropylidene-1,1-bisphosphonate (APD) orally, 250 mg daily, for periods of 2 months, alternating with periods of 2 months of abstinence. Total duration of therapy was 1 year. Radiological and clinical improvement was striking. Furthermore, X-rays of the bones showed large, parallel radio-opaque striae, corresponding exactly to the periods of therapy. These were present in all metaphyses.

The aim of this study was to assess whether early intermittent I.V. administration of disodium pamidronate can effectively achieve primary prevention of glucocorticoid-induced osteoporosis (GIOP). A total of 27 in- or outpatients who required first-time, long-term corticosteroid therapy at a daily dose of at least 10 mg prednisolone were studied. Patients were randomly selected to receive either pamidronate and calcium or calcium alone. Patients allocated to pamidronate treatment (pamidronate group) received a first intravenous infusion of 90 mg pamidronate simultaneously with the initiation of their steroid treatment. Subsequently, they received 30 mg pamidronate, intravenously, every 3 months, for as long as steroid therapy was continued. As with the control patients (calcium group), they were put on a daily 800-mg elemental calcium supplement given as calcium carbonate. Lumbar spine and hip (total and subregions) bone mineral densities (BMDs) were measured at the start and every 3-months by dual-energy X-ray absorptiometry (Hologic® QDR-2000). Over 1 year, the pamidronate group showed a significant BMD increase in the lumbar spine (3.6%), and at all sites of the hip (2.2% at the femoral neck). In the calcium group, a significant BMD reduction was registered at the lumbar spine (−5.3%) and at the femoral neck (−5.3%). Differences between the groups were significant at all sites measured. Intermittent intravenous pamidronate effectively achieves primary prevention of GIOP, as assessed by BMD measurements over 1 year.

In order to investigate the efficacy of ipriflavone (IP) on the prevention of vertebral fractures and the effect on bone mineral density (BMD) in women with postmenopausal osteoporosis, a large multicentric European study was designed and is presently ongoing. Included in the study were 460 Caucasian, nonobese postmenopausal women aged < 45 and < 75 years, menopaused for at least 12 months. Inclusion was on the basis of a lumbar bone mineral density (BMD) lower than 2 SD compared with healthy women aged 50 years, corresponding to values below 0.860 g/cm2(antero-posterior measurement) by Hologic QDR 1000. Women with prevalent vertebral fractures were excluded as well as those presenting secondary osteoporosis or having been treated with medications that could affect bone metabolism. This study was designed as a 3-year, doubleblind, placebo-controlled, parallel group study that randomized the women to the oral administration of either 3 × 200 mg/day of IP or placebo. All patients received a daily supplement of 500 mg calcium. The primary purpose of the study was to evaluate the efficacy of IP in preventing vertebral nontraumatic fractures. Fracture is defined here as a ≤20% decrease in any anterior, central, or posterior T4-L4 vertebral height. Blinded vertebral X-ray readings and vertebral morphometry have been centralized in an independent Center, with standardized evaluation of two experts. Power calculations have been based on the hypothesis that 21% of placebo-treated patients would fracture within 3 years and that treatment with IP would lead to a 50% reduction in the incidence of fracture. Statistical tests have been designed to have a power of 80%, with a type I error equal to 5%. Secondary endpoints were changes in vertebral, radial, and femoral BMD. Centralized controls on 100% BMD scans would ensure the good quality of BMD readings. This study should verify the hypothesis that IP significantly decreases the risk of vertebral fracture in postmenopausal, osteoporotic women.

Strontium ranelate is an orally active drug that may permit ongoing production of bone while at the same time reducing bone resorption. New vertebral fractures reportedly are less frequent in postmenopausal women who receive this agent. The Treatment of Peripheral Osteoporosis Study (TROPOS) is a randomized, double-blind, placebo-controlled trial designed to show whether strontium ranelate prevents nonvertebral fractures in European and Australian postmenopausal women who had a bone mineral density (BMD) equivalent to a T-score less than −2.5. Participants were 74 years or older, or 70 to 74 years if an additional fracture risk factor was present. Either strontium ranelate in a daily dose of 2 g or placebo was given to 5091 postmenopausal women with osteoporosis. Major statistical analysis was undertaken over 3 years of treatment. The intention-to-treat population totaled 4932 patients.

In most countries, calcitonin is available in the form of injections, and less frequently as an intranasal spray. An oral route of administration should improve compliance. In a preliminary feasibility study, we have compared the acute biological action of injectable salmon calcitonin (50 IU), with the injectable calcitonin analogue ASC 710 (0.2 mg) and oral ASC 710 (20 mg) in 6 patients suffering from active Paget's disease of bone. The intensity and duration of the biological response were not significantly different in the 3 modes of therapy. In conclusion, the oral calcitonin analogue ASC 710 possesses an antiresorbing activity in Paget's disease comparable to that of an injection of salmon calcitonin which demonstrates that it can cross the intestinal barrier.

SummaryThe authors report an unusual case of acute renal failure occurring in a patient with systemic lupus erythematosus and antiphospholipid antibodies. Kidney biopsy revealed glomerular thrombosis, in the absence of glomerulonephritis. The authors stress the clinical and biological signs that suggest the thrombotic nature of kidney failure in lupus patients.

We investigated whether serum titers of interleukin 10 (IL-10), a cytokine known to shift lymphocyte responses towards humoral immunity, reflect disease activity in systemic lupus erythematosus (SLE). Sera from 72 SLE patients, 25 RA patients and 30 healthy controls were tested for IL-10 by ELISA. Low titers of IL-10 were detected in the serum of 37.5% of SLE patients and in 24% of RA patients but in only 3% of healthy controls. Interestingly, serum IL-10 titers in SLE patients were positively correlated with the SLE Disease Activity Index (SLEDAI) and with anti-DNA antibody titers, but negatively with complement fraction C3 levels. These results indicate that serum IL-10 values reflect SLE disease activity and suggest that overexpression of IL-10 might play a pathogenic role in severe lupus disease.

&lt;it>Objective&lt;/it>. We previously described a novel radiolabelled monoclonal antibody &lpar;1.2B6&rpar;, which reacts with porcine E&hyphen;selectin, for targeting activated endothelium as a means of imaging inflammatory disorders, and presented initial clinical work based on 111In&hyphen;labelled antibody. The aim of the present study was to evaluate a Fab fragment of 1.2B6 labelled with 99mTc in patients with rheumatoid arthritis &lpar;RA&rpar; by comparison with &lpar;i&rpar; 111In&hyphen;labelled 1.2B6 F&lpar;ab′&rpar;&lt;inf>2&lt;/inf> and &lpar;ii&rpar; conventional bone scanning. &lt;it>Methods&lt;/it>. 99mTc&hyphen;1.2B6&hyphen;Fab &lpar;∼440 MBq&rpar; and 111In&hyphen;1.2B6&hyphen;F&lpar;ab′&rpar;&lt;inf>2&lt;/inf> &lpar;∼27 MBq&rpar; were compared in 10 patients using a double&hyphen;isotope protocol. Images were obtained 4 and 20–24 h after injection. Two normal volunteers were also imaged. In a separate group of 16 patients, 99mTc&hyphen;1.2B6&hyphen;Fab and 99mTc&hyphen;oxidronate &lpar;99mTc&hyphen;HDP&rpar; &lpar;∼740 MBq&rpar; were compared on the basis of visual and semi&hyphen;quantitative analysis of joint uptake &lpar;joint&sol;soft tissue ratios&rpar; 4 h after injection. The respective biodistributions and blood clearances of the two 1.2B6 fragments were also compared. &lt;it>Results&lt;/it>. Image contrast was slightly better with 99mTc&hyphen;Fab at 4 h but equal for the two tracers at 24 h. Diagnostic accuracy, taking joint tenderness or swelling as the clinical endpoint, was 76&percnt; for both fragments at 24 h. Plasma clearance of 99mTc&hyphen;Fab was faster than that of 111In&hyphen;F&lpar;ab′&rpar;&lt;inf>2&lt;/inf> &lpar;&lt;it>t&lt;/it>&lt;inf>1&sol;2&lt;/inf> 142 &lt;it>vs&lt;/it> 421 min; &lt;it>P&lt;/it>&lt;0.0001&rpar;. 99mTc&hyphen;Fab appeared somewhat unstable &lt;it>in vivo&lt;/it>, as shown by activity in the thyroid gland and bowel. The diagnostic accuracy of 99mTc&hyphen;Fab was 88&percnt;, higher than that of 99mTc&hyphen;HDP &lpar;57&percnt;&rpar; as a result of the low specificity of the latter in RA. Receiver operating characteristic &lpar;ROC&rpar; curve analysis using joint&sol;soft tissue ratios as a variable cut&hyphen;off showed that 99mTc&hyphen;Fab discriminates better than 99mTc&hyphen;HDP between actively inflamed and silent joints &lpar;&lt;it>Z&lt;/it>&equals;4.72; &lt;it>P&lt;/it>&lt;0.0001&rpar;. No uptake of 99mTc&hyphen;Fab was observed by inactive or normal joints, whereas 99mTc&hyphen;HDP was taken up by all joints to a variable degree, making the decision as to whether a particular joint is actively involved or chronically damaged very difficult. &lt;it>Conclusion&lt;/it>. 99mTc&hyphen;anti&hyphen;E&hyphen;selectin&hyphen;Fab scintigraphy can be used successfully to image synovitis with better specificity than 99mTc&hyphen;HDP bone scanning. The advantages over 111In&hyphen;1.2B6&hyphen;F&lpar;ab′&rpar;&lt;inf>2&lt;/inf> are easier availability of the radionuclide, improved physical properties and optimal imaging 4 h after injection.

Without Abstract:

Without Abstract:

Without Abstract:

Without Abstract:

Without Abstract:

Without Abstract:

Without Abstract:

Without Abstract:

We measured lumbar spine, hip (total and sub-regions) and total body bone mineral densities (BMDs) by dual-energy X-ray absorptiometry (DXA) in 47 premenopausal female patients suffering from systemic lupus erythematosus (SLE). As compared to healthy controls, SLE patients had lower BMDs at all trabecular and cortical sites. Comparison of BMDs between patients ever and never treated with glucocorticoids indicated that patients who had ever received glucocorticoids had a significantly lower lumbar spine BMD compared to those who never did. Moreover, bone loss in patients ever treated with glucocorticoids was commensurate with their cumulated oral glucocorticoid intake. Interestingly, patients never treated with glucocorticoids had a lower hip BMD compared to controls, thereby suggesting that the disease per se might induce some bone loss. Taken together, SLE patients suffer from a significant trabecular and cortical bone loss indicative of an increased risk of future fracture.