Does bone quality predict loosening of cemented total hip replacements?

We matched 78 patients with a loose cemented Charnley Elite Plus total hip replacement (THR) by age, gender, race, prosthesis and time from surgery with 49 patients with a well-fixed stable hip replacement, to determine if poor bone quality predisposes to loosening. Clinical, radiological, biomechanical and bone mineral density indicators of bone quality were assessed. Patients with loose replacements had more pain, were more likely to have presented with atrophic arthritis and to have a history of fragility fracture, narrower femoral cortices and lower peri-prosthetic or lumbar spine bone mineral density (all t-test, p < 0.01). They also tended to be smokers (chi-squared test, p = 0.08). Vitamin-D deficiency was common, but not significantly different between the two groups (t-test, p = 0.31) In this series of cemented hip replacements performed between 1994 and 1998, aseptic loosening was associated with poor bone quality. Patients with a THR should be screened for osteoporosis and have regular radiological surveillance.

Dual-function remotely-pumped Erbium-doped fiber amplifier: Loss and dispersion compensator.

An efficient Erbium-doped fiber amplifier configured in doublepass amplification scheme with chirped fiber Bragg grating as the reflector is presented in this paper. The proposed amplifier architecture is optimized and designed to work under consideration of low pump powers for remotely-pumped applications. The chirped fiber Bragg grating is used to reflect the amplified signal back to the Erbium-doped fiber and at the same time to compensate the effect of fiber dispersion. The proposed amplifier architecture is able to maintain gain of higher than 20 dB for small signals less than -23 dBm with 10 mW pump power only. The integrated function of loss and dispersion compensator in single black box is an attractive solution to be used as pre-amplifier.

Rectal steroids suppress bone formation in patients with colitis.

BACKGROUND: The aetiology of bone loss in inflammatory bowel disease is multifactorial, but oral corticosteroids are an important contributory factor. Rectally administered steroids are widely used in patients with distal disease, but very little is known about their effect on bone metabolism. The aim of this study was to investigate the effect of a standard course of rectal prednisolone on biochemical markers of bone turnover. METHODS: In a longitudinal study of 10 patients, biochemical markers of bone turnover were measured before, during and after treatment with prednisolone metasulphobenzoate (Predfoam, Pharmax Ltd) 20 mg twice daily for 2 weeks. Bone formation markers measured were serum osteocalcin (BGP), bone-specific alkaline phosphatase (BALP) and procollagen carboxy-terminal propeptide (PICP). Urinary deoxypyridinoline (dPyr) was measured to assess bone resorption. RESULTS: Disease activity scores improved during treatment (difference in mean Powell-Tuck score = 2.3 (+/-13.1), 95% CI: 0.11-4.48, P = 0.04). There was a significant fall in BALP (P = 0.02) during treatment, and a rapid but non-significant fall in BGP (P = 0.19). PICP (0.42), and urinary dPyr (0.30) did not change significantly during treatment. CONCLUSIONS: Following a standard 2-week course of rectal prednisolone metasulphobenzoate, we observed a significant fall in bone-specific alkaline phosphatase activity. These results suggest that bone formation is suppressed in patients with distal colitis treated with pharmacological doses of rectal steroids.

Sex hormone status and bone metabolism in men with Crohn's disease.

BACKGROUND: Men with Crohn's disease (CD) are at risk of osteoporosis, but the factors contributing to low bone mineral density and its optimum treatment have not been established. AIM: To investigate the sex hormone status of men with CD, and to establish the influence of sex hormones on their bone metabolism. METHODS: Bone density was measured by dual energy X-ray absorptiometry at the hip and lumbar spine in 48 men with CD. Total serum testosterone and gonadotrophins were measured in all subjects and the free androgen index calculated in men with low or borderline total testosterone. Serum osteocalcin, pro-collagen carboxy-terminal peptide, bone specific alkaline phosphatase and urinary deoxypyridinoline were measured as markers of bone turnover. RESULTS: Eight (17%) men had osteoporosis, and a further 14 (29%) had osteopenia. Three (6%) men had a low free androgen index and normal gonadotrophins consistent with secondary hypogonadism, two of whom had osteopenia of the hip and spine. Age (P = 0.002) and small bowel Crohn's disease (P = 0.02) were the only independent predictors of serum testosterone. There was a significant association between total testosterone and osteocalcin (r = 0.53, 95%, CI: 0.29-0.71, P = 0.0001) which was independent of age and current steroid use (P = 0.0001). CONCLUSIONS: Previously undiagnosed hypogonadism is an uncommon cause of low bone density in men with CD. The independent association between testosterone and the bone formation marker osteocalcin suggests sex hormone status influences bone metabolism in men with CD. The results suggest testosterone replacement might be effective treatment for some men with osteoporosis and Crohn's disease.

Increased bone resorption in patients with Crohn's disease.

BACKGROUND: Patients with Crohn's disease are at risk of osteoporosis and premature fracture. However, the pathophysiology underlying bone loss remains poorly understood and the optimum treatment has not been established. AIM: To investigate mechanisms of bone loss in Crohn's disease using biochemical markers of bone turnover. METHODS: Bone mineral density was measured at the hip and spine using dual-energy X-ray absorptiometry in 117 patients (48 male) with Crohn's disease. Bone turnover was assessed by measuring serum osteocalcin (BGP), pro-collagen carboxy-terminal propeptide (PICP), bone specific alkaline phosphatase (BALP) and urinary deoxypyridinoline (DPD); and compared to age-matched healthy controls (n = 28). RESULTS: Bone mineral density was reduced (z-score < -1) in 48 (41%) patients with Crohn's disease. Mean values for bone formation markers in patients with Crohn's disease were all within the normal reference range (BGP 8.92 (+/- 3.23) ng/mL (normal range 3.4-10.0), BALP 17.6 (+/- 12.6) U/L (normal range 11.6-43.3), PICP 95.1 (+/- 46.5) ng/mL (normal range 69-163)) and were not significantly different to the control population. However, mean urinary DPD was significantly higher in patients with Crohn's disease compared to healthy controls (10.97 (+/- 9.22) nM DPD/mM creatinine vs. 5.02 (+/- 1.03) nM DPD/mM creatinine, difference in means = 5.95, 95% CI: -9.6 to -2.3, P = 0.00001) and compared to the UK reference range DPD levels were increased in 74 (63%) patients. CONCLUSIONS: Bone resorption as evidenced by urinary DPD was frequently increased in patients with Crohn's disease and was significantly higher than in an age-matched control population. The high levels of urinary DPD suggest increased bone collagen degradation may contribute to osteoporosis in patients with Crohn's disease. These results suggest anti-resorptive agents such as the bisphosphonates may be effective treatment for osteoporosis in Crohn's disease.

The effect of rectally administered steroids on bone turnover: a comparative study.

BACKGROUND: Oral glucocorticoids contribute significantly to the risk of osteoporosis in patients with inflammatory bowel disease. Less well established are the effects of rectally administered steroids on bone metabolism. AIM: To investigate the effects of two widely used rectal foam preparations (prednisolone metasulphobenzoate and hydrocortisone acetate) on biochemical markers of bone turnover. METHODS: Twenty-four patients with active inflammatory bowel disease randomly received a standard course of either prednisolone metasulphobenzoate or hydrocortisone acetate for 2 weeks. Biochemical markers of bone turnover were measured before, during and after treatment. Bone formation markers measured were serum osteocalcin (BGP) and bone-specific alkaline phosphatase (BALP). Urinary deoxypyridinoline (DPD) was measured to assess bone resorption. RESULTS: Disease activity scores improved during treatment (difference in mean Powell-Tuck score = 3.4, 95% CI: 2.0-4.8, P < 0.0001) and were similar in both hydrocortisone and prednisolone-treated groups. There was no significant reduction in BALP or BGP during treatment with either steroid preparation, and urinary DPD did not change significantly during treatment. CONCLUSIONS: During a 2-week course of rectal hydrocortisone acetate or prednisolone metasulphobenzoate, there was no significant change in biochemical markers of bone formation or resorption. These results suggest that pharmacological doses of rectal steroid foam preparations do not significantly impair bone turnover in patients with inflammatory bowel disease.

Persistently raised serum acid phosphatase activity in a patient with hypophosphatasia: electrophoretic and molecular weight characterisation as type 5.

Hypophosphatasia is a rare disorder characterised by low levels of serum alkaline phosphatase activity resulting in abnormal phosphorylated metabolites and varying skeletal abnormality. We have followed a patient with adult type hypophosphatasia for over ten years who has also shown a persistently elevated tartrate resistant acid phosphatase activity (TRAP) without any obvious cause. Characterisation of this TRAP by polyacrylamide gel electrophoresis (pH 4.0) showed migration to band 5 position. Molecular weight determination by FPLC and an estimate of the molecular weight by gradient gel electrophoresis gave a molecular weight of 29,000-43,600. This molecular weight makes it unlikely for this to be a IgG/TRAP complex persisting in the circulation. Paranitrophenylphosphate was the preferred substrate. This characterises the enzyme as type 5 acid phosphatase which is of the mononuclear/phagocyte type, possibility of osteoclastic origin, though the tissue source remains unknown.

Neutrophil alkaline phosphatase (NAP) score in the diagnosis of hypophosphatasia.

Hypophosphatasia is an inherited disease characterised by low tissue non-specific alkaline phosphatase (TNSALP) levels and skeletal defects. Diagnosis is usually made by measurement of serum total alkaline phosphatase (TALP, reference range 40-130 iu/l) and pyridoxal-5'-phosphate (PLP), and urine phosphoethanolamine (PEA). Neutrophil alkaline phosphatase (NAP) scores (reference range 20-150) have been reported to be low in isolated cases, but no comparison has been made of the diagnostic value of NAP, TALP, PEA and PLP in hypophosphatasia. We undertook such a comparison in six families with hypophosphatasia. In four families (Families 1, 2, 5, 6) with the adult type of hypophosphatasia, inherited as autosomal dominant, the NAP score and TALP (<40 iu/l), were low, <20 and <40 iu/l respectively, in all affected subjects, though the PEA and PLP were not consistently abnormal. In one of the two families (Family 3) with the autosomal recessive type of hypophosphatasia an affected subject had low NAP as well as low TALP, PLP and PEA. In another family (Family 4) one of the heterozygotes had a low NAP while the other had a normal NAP score (45). A child in this family had a normal TALP level. Her low NAP score (15) supported her to be a possible heterozygote. NAP score is readily available from most laboratories and may be diagnostically helpful in hypophosphatasia.

Comparison of serum catalytic activity and immunoreactivity of bone alkaline phosphatase in hypophosphatasia.

Hypophosphatasia is a rare bone disorder characterised by low levels of tissue non-specific alkaline phosphatase (TNSALP). Although TNSALP is widespread in virtually all tissues the clinical effects, when produced, seem only to affect the mineralizing tissue such as teeth and skeleton. The skeleton is severely affected in the perinatal form of the disease, when death may occur in utero, or may not be affected in the adult type variety of the disease. We therefore compared the catalytic (cBALP) and immunoreactivity (iBALP) of bone alkaline phosphatase isoenzyme in six families with hypophosphatasia. iBALP was measured using an IRMA method. cBALP was measured after electrophoretic separation of serum alkaline phosphatase isoenzymes on lectin containing agarose gel. The percentage of different isoenzymes was calculated using densitometric scanning and cBALP calculated from the known total serum alkaline phosphatase activity. Results showed cBALP=0.796+3. 269iBALP, r=0.9 p<0.01, in cases of hypophosphatasia. In general, the lower the iBALP and cBALP the more severe the skeletal disease. The bone isoenzyme level predicts the clinical severity of bone disease.

Long-term results of unilateral neck exploration for preoperatively localized nonfamilial parathyroid adenomas.

BACKGROUND: Unilateral neck exploration for sporadic parathyroid adenomas remains a contentious policy. The morbidity is lower than for bilateral surgery, but the long-term outcome may be inferior. METHODS: The results of a policy of unilateral neck exploration for primary hyperparathyroidism based on preoperative localization are reviewed. RESULTS: Over a 10-year period, 89 patients were operated on, 57 undergoing unilateral neck exploration. Unilateral neck exploration significantly reduced operative time (P < 0.0001) and postoperative hypocalcaemia (P = 0.021). Over a mean biochemical follow-up of 38 months, recurrent hypercalcaemia occurred in 6% of patients, including 3.5% of those undergoing unilateral neck exploration, an additional 10% of patients were normocalcaemic with an inappropriately elevated parathormone level. CONCLUSIONS: A policy of unilateral neck exploration can achieve comparable long-term results to more extensive bilateral surgery.

The relation of hand skin-fold thickness to bone mineral density in patients with Crohn's disease.

OBJECTIVES: In healthy postmenopausal women, the association of skin-fold thickness (SFT) with bone mineral density (BMD) is well described, and a low SFT is a useful predictor of osteoporosis. In this study the association between hand SFT and BMD in patients with Crohn's disease was assessed; and the potential for hand SFT as a screening test for osteoporosis evaluated. DESIGN/METHODS: In a cross-sectional study, BMD was measured at the hip and lumbar spine by dual energy x-ray absorptiometry (DEXA). SFT was measured on the dorsum of the right hand using Holtain Tanner Whitehouse calipers. One hundred and seventeen patients (48 male) with Crohn's disease and 50 (25 male) controls were studied. RESULTS: There was a significant correlation between hand SFT and BMD (expressed as t scores) at all four measured sites (lumbar spine r = 0.41, P < 0.0001, 95% CI 0.25-0.55, Ward's triangle r = 0.38, P < 0.0001, 95% CI 0.21-0.53, trochanter r = 0.33, P < 0.0001, 95% CI 0.16-0.48, femoral neck r = 0.38, P < 0.0001, 95% CI 0.21-0.53). On stepwise regression analysis, the association remained significant after correcting for age, weight, menstrual status and current steroid use (P < 0.05). Hand SFT was significantly lower in patients with Crohn's disease than controls (difference in means 0.51 mm, 95% CI 0.3-0.72, P < 0.0001). Mean hand SFT was significantly lower in patients with osteoporosis compared to patients with normal BMD (difference in means 0.74 mm, 95% CI 0.33-1.15, P < 0.001), as was that of osteopenic patients compared to patients with normal BMD (difference in means 0.28 mm, 95% CI 0.01-0.55, P < 0.05). In the diagnosis of osteoporosis, the sensitivity of hand SFT ranged from 29% to 93%, with specificities of 54% to 95%. CONCLUSIONS: Hand SFT is independently associated with BMD in Crohn's disease and is lower than in age-matched healthy subjects. Hand SFT in combination with other easily measurable confounding variables might be useful in screening for osteoporosis in patients with Crohn's disease.

Screening for osteoporosis in Crohn's disease. A detailed evaluation of calcaneal ultrasound.

OBJECTIVES: To compare calcaneal broadband ultrasonic attenuation (BUA) and velocity of sound (VOS) in patients with Crohn's disease with an age-matched control population. The validity of BUA as a screening tool for osteoporosis was evaluated and the relationship between BUA and previous fracture studied. DESIGN: Cross-sectional study. BACKGROUND: Since patients with Crohn's disease are at risk of osteoporosis and premature fracture, routine assessment of bone mineral density (BMD) is recommended. Quantitative ultrasound of the calcaneum is an inexpensive and radiation-free means of assessing bone density which also provides information on bone microstructure. METHODS: BUA (dB/MHz) and VOS (m/s) were measured at the calcaneum (CUBAclinical, McCue Ultrasonics, Winchester, UK) and compared with bone mineral density at the hip and lumbar spine measured by dual-energy X-ray absorptiometry (DEXA); 100 patients (42 men) with Crohn's disease and 52 age-matched healthy controls (23 men) were studied. RESULTS: BUA was significantly reduced in patients with Crohn's disease compared with age-matched controls [76.53 dB/MHz (+/-17.3) vs 87.29 dB/MHz (+/-17.9), difference in means = 10.76, 95% CI -16.67, -4.85, P = 0.0004] and was significantly associated with BMD at the spine (r = 0.49, 95% CI 0.32, 0.63, P< 0.0001) and femoral neck (r = 0.54, 95% CI 0.38, 0.67, P < 0.0001). In the diagnosis of osteoporosis (t score <-2.5) BUA had a sensitivity of 66.7% at the femoral neck, with a specificity of 85.6%; sensitivity of BUA at the spine was 75% with specificity 89%. CONCLUSION: Patients with Crohn's disease have reduced BUA compared with an age-matched control population. Calcaneal BUA is significantly associated with BMD at the hip and spine but the correlation is insufficient to recommend ultrasound as a screening tool for DEXA.

Alkaline phosphatase isoenzymes and clinical features in hypophosphatasia.

Hypophosphatasia is an hereditary disease characterized by low activity of total serum alkaline phosphatase (TALP) accompanied by a range of skeletal diseases. We have measured the main circulating alkaline phosphatase isoenzymes--bone (BALP), liver (LALP), intestinal (IALP), placental (PALP)--in six families with hypophosphatasia, using kinetic and electrophorectic methods. Our observations show that patients with skeletal disease tend to have a very low BALP activity. Patients even with undetectable LALP activity do not appear to manifest any clinical complications. Patients also showed proportionately high IALP activity. Since the production of significant IALP activity is not a constant feature in all healthy individuals, it remains to be established whether the survival of one of these patients (IALP > 80% of TALP) depended on the presence of circulating IALP.

Comparison of serum osteocalcin with total and bone specific alkaline phosphatase and urinary hydroxyproline:creatinine ratio in patients with Paget's disease of bone.

Osteocalcin or bone Gla protein (BGP) is secreted by osteoblasts, and its serum concentration is elevated in a number of conditions with high bone turnover. A comparison of serum osteocalcin with total (TALP) and bone specific alkaline phosphatase (BALP) and urinary hydroxyproline/creatinine (OHP/Cr ratio) was performed in 13 patients with active Paget's disease of bone. BGP did not correlate significantly with either BALP or TALP, but did show a significant correlation with OHP/Cr ratio (r = 0.76; P < 0.01). BGP does not appear to be as sensitive a marker as BALP or TALP in Paget's disease.

Hormone status in patients with slipped capital femoral epiphysis.

In 15 consecutive patients with slipped capital femoral epiphysis we recorded height, weight and skeletal maturity. Sexual maturity was assessed clinically and biochemically, and Harris's hypothesis that there is an increased ratio of serum growth hormone to oestrogen was tested in comparison with 15 age and sex matched controls. We found no difference in skeletal or sexual maturity between the groups, or any overt endocrine abnormality in the patients. However almost half the patients with slipped epiphysis were over the 90th weight percentile, suggesting that mechanical factors such as obesity are more important aetiologically than endocrine abnormalities.

Prognostic indicators in tibial shaft fractures: serum creatinine kinase activity.

Serum creatinine phosphokinase (CPK) levels were measured serially in 50 adults with closed tibial shaft fractures. CPK activity increased significantly after fracture (p less than 0.001). High energy and slowly healing fractures had significantly higher levels than low energy and normally healing fractures, respectively. Thus, CPK determinations could be used to assess the severity of trauma and possibly prognosis in tibial shaft fractures.

Intraoperative parathyroid hormone estimation: a valuable adjunct to parathyroid surgery.

Serial measurements of serum intact parathyroid hormone (PTH) and adjusted total calcium levels were performed on 10 patients during unilateral neck exploration for a solitary parathyroid adenoma localised preoperatively by ultrasound scan. Frozen section was performed peroperatively to establish the presence of parathyroid tissue. Levels of PTH were shown to be within the normal range within 15 min of adenoma removal (a mean of 13.4% of their preoperative values), allowing clear early distinction from unsuccessful surgery where no change occurred. Frozen section wrongly identified thyroid tissue as parathyroid in one case leading to a failure of the initial neck exploration. Our findings show that intraoperative PTH measurements can accurately predict whether all hyperfunctioning parathyroid tissue has been removed. This is not always possible using frozen section techniques. The wider use of intraoperative PTH measurement, particularly in difficult cases, may avoid the need for prolonged explorations to identify all four glands and, perhaps, biopsy of normal glands, replacing the current standard use of frozen section as a more reliable indicator of the success of parathyroid surgery.

Comparison of 'intraoperative' parathormone measurement with frozen section during parathyroid surgery.

Intact parathyroid hormone (PTHi) has a relatively short half-life and levels fall significantly within 15 min of the successful excision of all the abnormal parathyroid glands during surgery for hyperparathyroidism. Monitoring this fall has been suggested as useful in decreasing the failure rate of neck explorations in parathyroid surgery. We have performed a comparative study of the use, during surgery for primary hyperparathyroidism, of routine frozen section with the recently available rapid assay for PTHi. The assay demonstrated a significant fall (P = 0.013) in the level of PTHi from a pre-excision mean of 26.66 pmol/l to 5.94 pmol/l 15 min after surgical excision. In all cases the level of PTHi fell to less than 30% of pre-excision levels by 30 min. However, while frozen section results were available in a mean time of 22 min after excision, the PTHi levels took a mean of 105 min. We conclude that during straightforward parathyroid surgery for primary hyperparathyroidism, the current assay does not offer any advantages over the already routine use of frozen section.

Does subclinical pancreatic inflammation occur after parathyroidectomy?

Pancreatitis is accepted as an uncommon complication of parathyroid surgery, but it has been suggested that up to 35% of patients may experience hyperamylasaemia after parathyroidectomy indicating subclinical inflammation of the pancreas. A series of 26 patients undergoing parathyroidectomy were studied by preoperative biochemical analyses repeated 24 and 48 h postoperatively allowing changes in calcium metabolism and serum and urinary amylase levels to be documented. Of the patients, 21 also underwent a CT scan of the pancreas between 24 and 48 h after operation. Despite highly significant changes in serum parathormone, calcium and phosphate levels postoperatively, there was no evidence in any patient of acute pancreatic inflammation or hyperamylasaemia. Twenty-one patients underwent unilateral neck exploration, and we suggest that the absence of any detectable amylase elevation supports the suggestion that such elevation may reflect an increase in salivary isoamylase as a result of extensive neck dissection, rather than reflecting a subclinical pancreatitis. The development of postparathyroidectomy pancreatitis appears to be an all or nothing phenomenon of unknown aetiology.