Alendronate-related femoral diaphysis fracture--what should be done to predict and prevent subsequent fracture of the contralateral side?

INTRODUCTION: Atypical fractures of the femoral diaphysis have recently been associated with alendronate therapy (Neviaser et al. J Orthop Trauma 22(5):346-350, 2008; Kwek et al. Injury 39:224-231, 2008; Lenart et al. N Engl J Med 358:1304-1306, 2008). METHODS: In many cases, fractures have occurred bilaterally prompting debate regarding appropriate screening of the unaffected side (Kwek et al. N Engl J Med 359(3):316-317, 2008). CASE REPORT: We report a case of sequential, bilateral, femoral diaphysis fractures associated with prolonged alendronate therapy and the failure to predict the subsequent fracture of the contralateral side despite radiological imaging. DISCUSSION: We review the current literature and discuss potential management strategies.

The interaction of sodium nitroprusside with peripheral white blood cells in vitro: a rationale for cyanide release in vivo.

Isolated monocytes and polymorphonuclear leukocytes release the cyanide anion from the hypotensive agent, sodium nitroprusside. The proposed mechanism involves the production of hydrogen peroxide which oxidizes the substitution inert d6 iron(II) transition metal complex to a labile d5 iron(III) complex. Consequently, the release of cyanide becomes more favoured. This mechanism is supported by the chemical release of the cyanide anion from sodium nitroprusside in vitro by hydrogen peroxide and the demonstrated ability of monocytes and polymorphonuclear leukocytes to generate hydrogen peroxide ex vivo when chemically stimulated by the nitroprusside anion. The results suggest that within a clinical environment white cell counts and cell activation induced as a consequence of disease processes may be important for predicting the toxicity of sodium nitroprusside.

Idiopathic destructive arthritis of the shoulder.

IDA of the shoulder is a condition found predominantly in elderly females. Although the shoulder is primarily involved, other joints such as the hip and knee can be affected, and concurrent OA is common at other joint sites. Clinical features include voluminous, often blood-stained effusions, together with features of rotator cuff rupture and restriction of shoulder movement. Laboratory parameters are usually normal and examination of the synovial fluid reveals large amounts of basic calcium phosphate crystals. The synovium is hypertrophied and vascular and shows fibrin deposition. It contains calcified material extracellularly. An acute inflammatory infiltrate is absent. Radiographs demonstrate soft tissue swelling and subchondral sclerosis with marked bony attrition involving the acromioclavicular and glenohumeral joints, as well as the humeral head and neck. Although some aspects of the disease seem distinct, many features are shared with other types of destructive arthritis of the shoulder. The pathogenesis of this disorder is at present obscure, but it is clear that an understanding of the processes involved will provide a vital contribution to our understanding of the response of the joint to insult. With a multidisciplinary approach and adequate communication between interested workers this aim could seen be within our grasp.

Site of action for the inhibition by gold sodium thiomalate of rabbit platelet activation.

The inhibitory action of the gold-based drug gold sodium thiomalate was investigated in rabbit platelets. Gold sodium thiomalate at concentrations of 0.25-13 x 10(-4) M inhibits collagen-, ADP-, and 9,11,dideoxy-11 alpha,9 alpha-epoxymethanoprostaglandin F2 alpha (U46619)-induced aggregation as well as collagen- and U46619-induced serotonin release. This inhibition occurs in both Tyrodes-albumin or Tyrodes-gelatin buffer systems. Preincubation of gold sodium thiomalate with platelets resulted in less inhibition as the time of preincubation increased. The inhibitory effect of gold sodium thiomalate could be removed by washing the platelets. Other sulfhydryl-reacting compounds, such as D-penicillamine, thiomalic acid, 5,5'-dithiobis-2-nitrobenzoic acid, and 6,6'-dithiodinicotinic acid, were all capable of inhibiting collagen-induced aggregation and serotonin release. Evidence is presented that gold sodium thiomalate interferes with the activation of rabbit platelets by several activators, that this action of gold sodium thiomalate is similar to the action of other sulfhydryl-reacting agents, that this inhibition is likely occurring at the membrane, and that the action of the drug is not dependent on the presence of albumin.

Acute vasculitis resulting in free flap failure: the importance of early recognition and options for management.

Unusual or unexpected medical causes for free flap failure do occur but are uncommon. We present a rare case of a fibula free flap failure due to an acute vasculitis which was undiagnosed until after the flap had failed. In addition to two successful flap salvages and intravenous heparin, an epoprostenol infusion was commenced but a third salvage was not successful. The vasculitis resulted in marked blood vessel wall thickening, and cutaneous manifestations which presented as late signs. High peri-nuclear anti nuclear cytoplasmic antibody (pANCA) and myeloperoxidase (MOP) titres were subsequently found and histology from several blood vessels showed marked inflammation throughout the wall. A diagnosis of microscopic polyangiitis was made and high dose steroids were subsequently commenced. Interestingly, he had vasculitis several years previously treated with oral steroids but had been discharged from the rheumatology clinic. This rare case illustrates the potential hazards of free flap surgery in the vasculitides and discusses the warning signs and various management options to reduce the likelihood of flap failure in these patients.

Scintigraphic assessment of osteoarthritis of the knee joint.

Clinical, radiographic, and scintigraphic abnormalities of the knee joint have been correlated in a cross sectional study of 100 patients with osteoarthritis. The group comprised 73 women and 27 men with a mean age of 65.7 years. One hundred and ninety one of the 200 knees had clinical (175) or radiographic (185) evidence of osteoarthritis, or both (161). Scintigraphic images of the knees were obtained 4-5 minutes (early phase) and 2.5-3.5 hours (late phase) after intravenous injection of 600 mBq of technetium-99m diphosphonate. Abnormal images were recorded in 162 knees (81%), and six different patterns were detected. Generalised isotope retention around the knee (early or late phase) was less common than focal areas of uptake around the joint margin (early or late phase) or in the patella or subchondral bone (late phase). Some knees with abnormal scans were normal on radiography (n = 7), or vice versa (n = 21). Different scan patterns correlated with different clinical and radiographic features: the generalised pattern correlated with pain (odds ratio (OR) = 45.1) and osteophytes (OR = 48.3); joint line retention correlated with subchondral bone sclerosis on radiography (OR = 62.1); and subchondral bone retention correlated with more severe radiographic changes. It is concluded that different patterns of scintigraphic abnormality reflect various aspects of the disease process of osteoarthritis.

Congenital malformations associated with anencephaly in the Fylde peninsula of Lancashire.

The necropsy reports of 174 cases of anencephaly, born in the Fylde peninsula of Lancashire between 1957 and 1980, have been analysed for the presence of other malformations. The results were compared with a similar previous series from Bristol, though the Bristol study differed both in time (1948 to 1975) and in the fact that it was hospital based and, unlike the present study, did not achieve near complete ascertainment. Of the Lancashire anencephalics, 24% had other malformations, a significantly lower rate than in the Bristol series. There was a much higher rate of renal and urinary tract defects in the Bristol series, and a higher rate of cardiovascular defects in the Lancashire series. The distribution of associated malformations differed in the two areas, possibly representing different patterns of aetiological heterogeneity. The iniencephaly rate was so much lower in Lancashire as to suggest an artefact, perhaps owing to the lack of a precise definition of the condition.

Magnetic resonance imaging in osteoarthritis of the knee: correlation with radiographic and scintigraphic findings.

Twelve knees with a range of severity of knee osteoarthritis were assessed by magnetic resonance imaging (MRI) and technetium-99m labelled hydroxymethylene diphosphonate scintigraphy. Five magnetic resonance pulse sequences were evaluated. Proton density (TR = 1000, TE = 26 ms) and STIR (TR = 1500, TI = 100, TE = 30 ms) were chosen for further use. Abnormalities shown by MRI included joint effusions, meniscal disruption, hyaline cartilage thinning, subchondral signal changes, pseudocysts, and heterogeneity of signal from osteophytes. Certain MRI and scintigraphic appearances correlated: (a) 'hyperintense osteophytosis' and ipsilateral 'tramline' scintigraphic uptake, suggesting increased fat content in 'active' osteophytes; (b) subchondral signal change and 'extended' pattern, possibly reflecting inflammation, synovial leak, or fibrovascular repair; (c) patellofemoral joint signal changes and patellar isotope uptake.

A two-year, placebo-controlled trial of non-steroidal anti-inflammatory therapy in osteoarthritis of the knee joint.

Eighty-nine patients with established OA of the knee joint, already on regular NSAIDs for joint pain, were randomly allocated to receive 100 mg/day of slow release diclofenac (45 patients) or matching placebo (44), in place of their NSAID, for 2 years. Thirty-eight patients withdrew or dropped out of the study. The major causes for withdrawal were lack of efficacy (three active, 12 placebo, P < 0.01) or side effects (six active, five placebo), and most withdrawals occurred within the first 6 months. Long term follow up of these patients was not possible. Fifty-one patients completed the study (31 active, 20 placebo), 35 of whom reported that they were the same or better at the end of the 2-year period than at the beginning. Most of the recorded clinical parameters showed little or no change over 2 years in these 51 subjects, and in 70% there was no detectable change in the radiographs. We conclude that long term placebo-controlled trials are both feasible and ethical in knee OA, but that conventional clinical and radiographic techniques detect very little change in joint structure or function over a 2-year time period. This may reflect the insensitivity of the methods used to assess progression rather than absence of change. The fact that 20 of 44 patients changed from an NSAID to placebo completed the 2-year study without any symptomatic penalty indicates that not all patients entered needed or responded to NSAIDs.

Clinical assessment of osteoarthritis of the knee.

The repeatability of physical signs used to assess osteoarthritis of the knee has not been systematically examined. The within and between observer variation of 10 commonly used physical signs to determine osteoarthritis of the knee has been assessed here. The results obtained show variation in the repeatability of these signs. For those examining the tibiofemoral joints the repeatability was greater than for those examining the patellofemoral joint. It would therefore seem vital to take note of the repeatability of physical signs in determining the number of subjects to be studied in epidemiological studies and therapeutic studies in osteoarthritis.

Levels of keratan sulfate in the serum and synovial fluid of patients with osteoarthritis of the knee.

We examined the relationship between serum and synovial fluid (SF) levels of antigenic keratan sulfate (KS) and the clinical, laboratory, and radiologic features of disease in 125 well-characterized patients with knee osteoarthritis (OA). KS was quantified by enzyme-linked immunosorbent assay, using an antibody specific for a highly sulfated epitope on KS chains; the results were calculated as equivalents of an international standard of KS from human costal cartilage. The mean level of serum KS (393 ng/ml) was significantly higher than those previously reported for populations of adults without OA. There was a wide scatter of serum KS values (range 156-912 ng/ml), with little correlation with clinical or radiologic features. Men had significantly higher levels than women (456 +/- 135 ng/ml versus 368 +/- 110 ng/ml, mean +/- SD), and there was a statistically significant but weak association with indicators of polyarticular involvement (number of symptomatic joints, Heberden's nodes, hip symptoms) in women. Despite the wide scatter of results in the population as a whole, individual levels of KS were stable for up to 4 consecutive years in the 9 patients studied. Levels of KS were much higher in SF (n = 25) than in serum, but the two were not correlated. There was an inverse correlation between radiographic evidence of cartilage loss and the level of KS in SF. The large variations in serum KS values suggest that this measure may not be of diagnostic significance among populations of patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Radiographic assessment of the knee joint in osteoarthritis.

The development of radiographic systems for the grading of osteoarthritis requires knowledge of the reproducibility of their individual component features. This paper reports the reproducibility, both within and between observers, for five commonly used radiographic features of osteoarthritis in the tibiofemoral and patellofemoral compartments of the knee joint. The results suggest that assessments of joint space narrowing, osteophyte, and bony contour in the tibiofemoral compartments are more reproducible than those of sclerosis and cyst. Patellofemoral assessments, with the exception of osteophyte, are considerably less reproducible between observers than tibiofemoral assessments.

Chrysiasis revisited: a clinical and pathological study.

Chrysiasis is a distinctive and permanent pigmentation of light-exposed skin resulting from the administration of parenteral gold salts. We report a study of 40 Caucasian patients with rheumatoid arthritis, treated with intramuscular sodium aurothiomalate, of whom 31 had chrysiasis. Visible changes develop above a threshold, equivalent to 20 mg/kg gold content, and their severity depends upon cumulative dose. Focal aggregates of particulate gold are deposited in the reticular and papillary dermis in amounts that correlate with the degree of pigmentation. Characteristically, initially the periorbital region is affected by a mauve discoloration, which intensifies and deepens into a blue/slate-grey colour, while extending to involve the face, neck and upper limbs. Although chrysiasis develops insidiously and patients may be unaware of the changes, positive identification is important in order to avoid misdiagnosis and medical mismanagement, and afford appropriate reassurance. Prevention is difficult, but measures to reduce sunlight exposure may be helpful.

The prevention of corticosteroid-induced bone loss with intermittent cyclical etidronate.

A prospective, randomised, double-blind, placebo controlled primary prevention trial was undertaken in 28 patients commencing low to moderate doses of corticosteroids for the first time. Patients were randomised to intermittent cyclical etidronate (400 mg daily for 2 weeks) and calcium (500 mg daily for 11 weeks) or intermittent cyclical placebo with calcium. After 52 weeks of treatment, lumbar spine BMD increased by 1.8% in the etidronate group, while it decreased by 3.7% in the placebo group. The differences in bone loss rate were statistically significant (p<0.01) at both 6 and 12 months. Similar trends were observed at the proximal femur, but differences were not statistically significant. These results suggest that intermittent cyclical etidronate therapy is effective in the primary prevention of corticosteroid-induced bone loss at the lumbar spine.

Concentration and reactivity of the sulphydryl group population on the membrane of intact erythrocytes in patients with rheumatoid arthritis.

The sulphydryl population on erythrocyte membrane is shown to vary as a function of the nutritional status of the cell. When an assay based on reaction with Ellman's reagent and controlled conditions were used the mean values (SEM) for the sulphydryl population on the membranes of normal erythrocytes incubated overnight in the presence and absence of glucose were found to be 3.29 (0.27) and 2.56 (0.25) million sulphydryl functions per cell respectively. Under identical conditions rheumatoid erythrocytes incubated in the presence and absence of glucose were found to have a significantly lower sulphydryl population--1.54 (0.08) and 1.15 (0.08) million respectively. The predominant concentrations of sulphydryl groups on the membrane are found at sites on the transmembrane proteins and, in particular, on the hexose transport protein. By influencing the nutritional status of the cells significant differences in activity between the normal and diseased state have been identified and these may have a role in the aetiology of rheumatoid arthritis by altering the response of cells to oxidative stress.

Reasons for late detection of hip dislocation in childhood.

A retrospective study of 56 children with dislocation of the hip presenting late found that the mean age at which the parents first noticed that something was wrong (including hip abnormalities found at birth in 10 patients) was 11 months, but that at diagnosis was 26 months, a mean delay of 15 months. The reasons for delay were failure to examine the hips at birth (13 cases), failure to follow up abnormalities at birth (7), failure of symptoms noticed by the parents to alert the health-care professional to the possibility of a dislocated hip (36), failure to check the hips routinely after 3 months (27), and failure of the parents to appreciate the significance of abnormalities and to act on them (28). Hip screening should continue beyond the neonatal period and should include routine checks on all children until they are walking normally. A greater awareness in health-care professionals of the features of hip dislocation and further health education for parents are needed.