An open, randomized, controlled study of transdermal hormone replacement therapy on the rate of bone loss in primary biliary cirrhosis.

OBJECTIVES: The prevalence of osteoporosis amongst patients with primary biliary cirrhosis (PBC) is high and may be a serious clinical problem. Hormone replacement therapy (HRT) is effective in preventing bone loss but has not been evaluated in randomized trials in PBC. The primary aim was to study the effect of transdermal HRT in combination with daily vitamin D and calcium supplementation on bone loss compared with vitamin D and calcium supplementation only in postmenopausal women with PBC. The secondary aim was to study the safety of transdermal HRT. SUBJECTS/INTERVENTIONS: Eighteen females with PBC were randomized to receive 2 years therapy with either (i) transdermal oestradiol 50 microg 24 h(-1) two times per week + medroxyprogesterone 2.5 mg day(-1) + alfacalcidol 0.25 microg day(-1) and calcium 1 g day(-1) or (ii) alfacalcidol 0.25 microg day(-1) and calcium 1 g day(-1). Dual-energy X-ray absorptiometry for measurement of bone mineral density (BMD) and sampling of blood and serum for measurements of biochemical markers of liver function was performed before, during and at the end of treatment. RESULTS: BMD increased significantly at the lumbar spine (P < 0.05) and the femoral neck (P < 0.05) in the HRT group whereas no significant change was found in the control group. One oestrogen-treated patient was excluded after 1 year because of deteriorating, but reversible, aminotransferases. Dropout frequency because of nonliver-related causes was higher in the HRT group. Otherwise, no difference with respect to adverse liver reactions was found between the groups. CONCLUSION: Transdermal HRT increases BMD in PBC patients with few severe side effects related to the liver.

The significance of radiolucent zones surrounding pedicle screws. Definition of screw loosening in spinal instrumentation.

We examined the radiographs from a prospective clinical study of fixation by pedicle screws and those from an experimental study in a sheep model. In the clinical study, instruments were removed from 21 patients after implantation for 11 to 16 months and the extraction torques of the screws were recorded. A structured protocol was used for the radiological examinations. In the experimental study, loaded pedicle screw instrumentations were implanted in the sheep for six or 12 weeks. After radiological examination the pull-out resistance and the histological characteristics were studied. In the clinical study, all screws with radiolucent zones had a significantly reduced mean extraction torque compared with screws without radiolucent zones (16 +/- 10 Ncm v 403 +/- 220 Ncm; p < 0.0001). In the experimental study the mean maximum pull-out resistance for the screws with radiolucent zones was significantly lower than for those with no radiolucency (243 +/- 156 N v2214 +/- 578 N; p = 0.0006) and the mean bone-to-screw contact was reduced for screws with zones compared with those without zones (8 +/- 9% v 55 +/- 29%; p = 0.0002). Our findings showed that all screws with radiolucent zones had low extraction torques or low pull-out resistance. A radiolucent zone is a good indicator of loosening of a pedicle screw.

Hydroxyapatite coating improves fixation of pedicle screws. A clinical study.

We investigated the effects of hydroxyapatite (HA) coating on the purchase of pedicle screws. A total of 23 consecutive patients undergoing lumbar fusion was randomly assigned to one of three treatment groups. The first received uncoated stainless-steel screws, the second screws which were partly coated with HA, and the third screws which were fully coated. The insertion torque was recorded. After 11 to 16 months, 21 screws had been extracted. The extraction torque was recorded. Radiographs were taken to assess fusion and to detect loosening of the screws. At removal, the extraction torques exceeded the upper limit of the torque wrench (600 Ncm) for many HA-coated screws. The calculated mean extraction torque was 29 +/- 36 Ncm for the uncoated group, 447 +/- 114 Ncm for the partly-coated group and 574 +/- 52 Ncm for the fully-coated group. There were significant differences between all three groups (p < 0.001). There were more radiolucent zones surrounding the uncoated screws than the HA-coated screws (p < 0.001). HA coating of pedicle screws resulted in improved fixation with reduced risk of loosening of the screws.

Cervical spine degeneration in fighter pilots and controls: a 5-yr follow-up study.

At 5 yr after MRI of the cervical spine, for evaluation concerning degenerative lesions, follow-up MRI was performed on asymptomatic experienced military high performance aircraft pilots (mean age 47 yr; mean accumulated flying time 3,100 h) and on age-matched controls without military flying experience. Young military high performance aircraft pilots (mean age 28 yr, mean accumulated flying time 915 h) were also re-examined. Compared with baseline MRI 5 yr earlier, there was significant increase in disk protrusions in all groups, in osteophytes in controls, and in foraminal stenoses in experienced pilots, and a significant reduction in disk signal intensity in young pilots. The difference between experienced pilots and controls was markedly reduced compared with that at baseline MRI. Thus, military high performance aircraft pilots seem to be at increased risk of premature development of degenerative lesions of the same type as are seen in an aging population. With increasing age the difference between pilots and controls diminishes.

DXA of the hip and heel ultrasound but not densitometry of the fingers can discriminate female hip fracture patients from controls: a comparison between four different methods.

Dual-energy X-ray absorptiometry (DXA) of the proximal femur and in more recent years quantitative ultrasound (QUS) of the heel are the most established methods for assessing hip fracture risk. Measurement of the fingers offers a new approach. We performed DXA of the proximal femur, QUS of the heel and fingers, and radiographic absorptiometry (RA) of the fingers in 87 non-institutionalized women, 65-85 years of age, with a first hip fracture and compared them with 195 randomly selected age-matched controls. Bone mineral density (BMD) of the femoral neck and heel Stiffness Index were significantly lower among cases than among controls (by 15% and 17%, respectively; p < 0.0001), whereas no significant differences were found for finger measurements. When applying the WHO criterion of osteoporosis, 62-98% of the patients were classified as osteoporotic, compared with 19-85% of the controls, depending on method and site. The risks of hip fracture, estimated as odds ratios for every 1 SD reduction in femoral neck BMD, heel Stiffness Index, finger QUS and finger RA, were: 3.6 (95% CI 2.4-5.5), 3.4 (95% CI 2.2-5.0), 1.0 (95% CI 0.7-1.3) and 1.2 (95% CI 0.8-1.6), respectively. Compared with women with normal BMD of the femoral neck, those classified as osteopenic had an odds ratio of hip fracture of 14 (95% CI 2-110), whereas those classified as osteoporotic had an odds ratio of 63 (95% CI 8-501). We conclude that hip DXA and heel QUS have similar capacities to discriminate the risk of a first hip fracture, whereas QUS and RA of the phalanges seem inferior techniques for differentiating female hip fracture patients from controls.

Cauda equina syndrome as a postoperative complication in five patients operated for lumbar disc herniation.

STUDY DESIGN: A retrospective analysis of records and radiographs in five patients who developed acute cauda equina syndrome after surgery for lumbar disc herniation. OBJECTIVES: To postulate as a possible pathophysiologic mechanism the venous congestion caused by preexisting spinal stenosis and to present a management plan: extended decompression within 48 hours. SUMMARY OF BACKGROUND DATA: Cauda equina syndrome is reported as a sequela in 0.2%-1% of the surgeries for lumbar disc herniation. There is, however, no consensus on the possible pathophysiologic mechanism to the complication or to its management. METHODS: Preoperative investigations consisted of magnetic resonance imaging, or myelography and computed tomography. There was a good correlation between clinical appearance and radiographic findings in all patients. When the complication became apparent in four of the patients, they were investigated with magnetic resonance imaging and reoperated on within 48 hours with wide decompressions. RESULTS: The index operation was reported uneventful in all patients. Postoperative magnetic resonance imaging did not show the cause of the cauda equina syndrome, nor could this be established at the reoperation. Before surgery, all five patients had preexisting narrowing of the spinal canal. In no case was the lumbosacral disc the index level. Two patients recovered fully, whereas the other three experienced varying degrees of residual symptoms. There was no correlation between the end result and the delay until secondary decompression. CONCLUSION: Relative spinal stenosis may contribute to the development of cauda equina syndrome after surgery for lumbar disc herniation. A venous congestion can be triggered by postoperative edema, leading to nerve root ischemia. The treatment of choice seems to be extended decompression within 48 hours.

Serum bone markers after intramedullary fixed tibial fractures.

Serum levels of bone markers were measured prospectively for 1 year in 30 adult patients with an intramedullary fixed tibial fracture. In a double blinded design, half of the patients received low intensity ultrasound. All fractures healed, although in seven of 30 the healing was delayed more than 6 months. There was no significant difference in radiologic healing time between the ultrasound group (median, 113 days) and the placebo group (median, 112 days). The marker for bone resorption, crosslinked telopeptide, peaked at 1 to 4 weeks, whereas markers for bone formation peaked at 10 to 16 weeks for bone specific alkaline phosphatase and osteocalcin. Crosslinked telopeptide was lower at 1 week in patients treated with ultrasound than in those receiving placebo. Patients with delayed healing did not differ in crosslinked telopeptide compared with patients with normal healing. There were no differences in bone formation markers between patients who received ultrasound or placebo. Patients with delayed healing had lower levels of bone specific alkaline phosphatase between 4 and 7 weeks than did patients with normal healing, although no such differences were seen for osteocalcin. The results indicate that low intensity ultrasound might slow bone resorption, although there is no visible effect on bone formation. Patients with delayed healing had adequate bone resorption but slower early bone formation than did patients with normal healing.

MRI cervical spine findings in asymptomatic fighter pilots.

MRI of the cervical spine for evaluation concerning degenerative lesions was performed on asymptomatic experienced military high performance aircraft pilots (mean age 42 yr with mean accumulated flying time of 2600 h), and for comparison on age-matched controls without military flying experience. Young military high performance aircraft pilots (mean age 23 yr with 220 h of flying per person) were also examined. There were significantly more osteophytes, disk protrusions, compressions of the spinal cord and foraminal stenoses in the experienced pilots than in the age-matched controls. Low frequency of low grade degenerative lesions was found in the young and inexperienced pilots.

No effect of low-intensity ultrasound on healing time of intramedullary fixed tibial fractures.

OBJECTIVE: To determine whether stimulation with low-intensity ultrasound will reduce the radiologic healing time of fresh tibial shaft fractures fixed with a reamed and statically locked intramedullary rod. DESIGN: Prospective, randomized, double blinded, and placebo controlled. PATIENTS AND METHODS: Thirty-two adult patients were included, fifteen in the active ultrasound group and seventeen in the placebo group. They all used an ultrasound device twenty minutes daily for seventy-five days without knowing whether it was active or inactive. Standardized radiographs were taken every third week until healing and at six and twelve months. All radiographs were assessed blinded and independently by a radiologist and an orthopaedic surgeon. The codes were not broken until all fractures had healed and all radiographs had been evaluated. RESULTS: The time until the first visible callus averaged 40+/-3 days for the active group and 37+/-3 days for the placebo (p=0.44). The healing time, defined as radiologic bridging of three cortices, was on average 155+/-22 days (median 113 days) for the active treatment group and 125+/-11 days (median 112 days) for the placebo group (p=0.76) as assessed by the radiologist and 128+/-13 days for the active group and 114+/-9 days for the placebo group (p=0.40) as evaluated by the orthopaedic surgeon. CONCLUSION: We conclude that low-intensity ultrasound treatment did not shorten healing time in fresh tibial fractures treated with a reamed and statically locked intramedullary nail. Our results are not in accordance with previous findings reporting reduced healing time in nonoperatively treated tibial shaft fractures when subjected to ultrasound.

Oral isotretinoin therapy in severe acne induces transient suppression of biochemical markers of bone turnover and calcium homeostasis.

Although dietary vitamin A is required for normal growth and development, long-term or high-dose administration of vitamin A derivatives (retinoids) may produce a variety of skeletal side-effects in man. In this study we investigated the early effects of oral isotretinoin therapy on bone turnover and calcium homeostasis in eleven consecutive patients with nodulocystic acne. The effects on bone metabolism were correlated to radiological and bone mineral density measurements following drug therapy for six months. Markers of bone turnover, i.e. serum osteocalcin, the carboxyterminal propeptide of type I collagen, bone specific alkaline phosphatase, the carboxyterminal telopeptide of type I collagen, and urine levels of calcium and hydroxyproline decreased significantly within five days of treatment (p < 0.05). There was also a statistically significant decrease in serum calcium, with a minimum on day five, and a marked increase in serum parathyroid hormone (p < 0.05). With continued treatment, however, the abnormal levels of these markers returned to baseline values within 14 days. No significant roentgenological changes or effects on bone mineral density were found in response to the drug. The observed inhibitory effects of isotretinoin on bone turnover, despite elevated parathyroid hormone levels, indicates that the drug exerts a direct effect on bone tissue.

Skeletal metastases from breast cancer: uptake of 18F-fluoride measured with positron emission tomography in correlation with CT.

OBJECTIVE: To characterise the uptake of 18F in skeletal metastases from breast cancer using positron emission tomography (PET) and to relate these findings to the appearance on CT. PATIENTS AND DESIGN: PET with 18F and CT were performed in five patients with multiple skeletal metastases from breast cancer. The CT characteristics were analysed in areas with high uptake on the PET study. Dynamic PET imaging of the skeletal kinetics of the 18F-fluoride ion were included. RESULTS: The areas of abnormal high accumulation of 18F correlated well with the pathological appearance on CT. Lytic as well as sclerotic lesions had markedly higher uptake than normal bone, with a 5-10 times higher transport rate constant for trapping of the tracer in the metastatic lesions than in normal bone. CONCLUSION: PET with 18F-fluoride demonstrates very high uptake in lytic and sclerotic breast cancer metastases.

Pathoanatomical and radiographic findings in spinal breast cancer metastases.

Spine specimens infested with breast cancer metastases, ranging from localized seed of small tumor deposits to massive invasion and vertebral collapse, were frozen in situ, removed, examined with both conventional radiography and high resolution computed tomography (CT), and then studied in great detail by serial cryoplaning. The majority of metastases in the total of 53.5 vertebrae were lytic, and most were in close contact with the vertebral wall or the endplates. Depressions and defects of the endplates were associated with compensatory expansion of the intervertebral discs. Although lytic lesions abutting endplate defects had the radiological appearance of metastases, all contained herniated disc material rather than tumor. Only four of the 29 grossly destroyed and collapsed vertebrae showed extrusion of the posterior vertebral wall into the spinal canal. Tumor growth in the epidural space was rare. There were no macroscopical reactive changes of the osseoligamentous or neurovascular spinal elements to the metastases, but abnormalities of the posterior elements (kissing spines, facet joint subluxation, and pars interarticularis failure) were common.

Clinical and experimental imaging of breast cancer metastases in the spine.

An investigation was undertaken to determine the characteristics of spinal breast cancer metastases with respect to MR signal intensity (SI), patho-anatomy and uptake of the bone-seeking radionuclide 18F measured with positron emission tomography (PET). Patients with spinal metastases from breast cancer, or spinal specimens, were examined with MRI and the results were correlated to histopathological findings, or they were examined with conventional radiography and CT in correlation with cryomicrotomical images, with CT and dynamic 18F-PET; or with MRI, CT, skeletal scintigraphy and conventional radiography, compared with one another. Metastases were detected in all anatomical parts of the vertebrae. The areas with bone marrow replacement by tumour were larger in the cryosectional images than was apparent on CT. Metastases were often in contact with the vertebral cortex or end-plates, and fractures occurred in destructive lesions. Neurovascular compromise was detected only at few levels and was caused by vertebral collapse rather than epidural tumour growth. Metastases (in vivo) displayed low SI on T1-weighted, low or intermediate SI on proton density-weighted, and high or intermediate SI on T2-weighted and "phase contrast" images, except for highly sclerotic metastases, which showed low SI on all sequences. Sensitivity was high and specificity limited since connective tissue in the vertebrae and bone marrow with high cellularity had similar SI. Both MRI and CT were more sensitive than conventional radiography and skeletal scintigraphy for revealing metastases in the cervical spine. On PET there was an increased uptake of 18F in metastases, both in osteosclerotic lesions and in osteolytic defects in the bone. Post-mortem MR examinations showed different SIs than MRI in vivo. The T1-and T2-relaxation times and SI were dependent on tissue temperature. Reversal of contrast between some tissues occurred at 5 degrees C in T1-weighted images.

Detection of breast cancer metastases in the cervical spine.

Thirty women with breast cancer and indications of possible cervical spine metastases underwent skeletal scintigraphy, conventional radiography, MR imaging and CT. By combining all examinations a diagnosis was settled in each patient and the different imaging techniques were compared. For all of the 26 patients with metastases in the cervical spine the correct diagnosis was found with MR imaging and CT. Both modalities also revealed paravertebral tumour growth, MR (n = 8) more than CT (n = 3). The sensitivity of skeletal scintigraphy in detecting metastases in the cervical spine was rather low, but as these examinations cover the whole body they are still convenient screening procedures, and combined with conventional radiography of selected areas are probably sufficient in many cases. Supplementary examinations with CT or MR would be valuable in patients with equivocal findings at screening for metastases or with clinical indications of metastases that remain unexplained after scintigraphy and radiography.

MR imaging with histopathological correlation in vertebral metastases of breast cancer.

In 5 patients with advanced breast cancer and spinal metastases MR imaging of the spine was performed before and/or after death. T1-, proton density-, and T2-weighted and "phase contrast" images were obtained in the sagittal plane. Autopsies included histopathologic examination of whole sagittal sections of the vertebral body. The relative signal intensities on the different MR sequences of various tissues identified histologically were evaluated. "Phase contrast" images combined with T1-weighted images were highly sensitive in detecting metastases. All metastatic tumours over 3 mm in size were found with MR imaging. Vertebrae containing connective tissue and reactive bone marrow had an MR appearance similar to that of metastases even though no metastases were found histopathologically.

Locking screw-plate fixation of cervical spine fractures with and without ancillary posterior plating.

Forty consecutive patients with 19 fractures and 21 fracture-dislocations in the lower cervical spine were treated prospectively with open reduction and interbody fusion, using the AO titanium locking screw-plate system. There were 30 men and 10 women with a mean age of 36 years (range 16-90 years). Eight were admitted tetraplegic, 12 tetraparetic, and 6 had nerve root injuries. Eleven of the fractures and 18 of the fracture-dislocations were also plated posteriorly. Complications included two cardiac arrests, two transient neurological impairments, two severe gastrointestinal bleedings, and one esophageal fistula. At 2-year follow-up, three patients had died and one had emigrated. Three out of ten patients who had complete motor loss initially had regained useful muscle function, while incomplete motor loss usually returned to normal. All fusions had healed in a good or acceptable position. Twenty-four of the 60 posterior plates impinged on facet joints and five were loose. Six screws transgressed facet joints below the fusion. Ten posterior fusions extended to adjacent mobile segments by exuberant bony overgrowth. Ancillary posterior plating significantly reduced the range of neck mobility and also caused significantly more pain than anterior plate fixation alone.

Diagnostic methods in planning palliation of spinal metastases.

In a prospective study of 30 patients with newly diagnosed spinal metastases the benefit of different imaging techniques in planning palliation was studied. Magnetic resonance imaging (MRI) was compared to scintigraphy, conventional radiography and computerized tomography (CT), prior to radiotherapy or surgery. In the first comparison, a total of 159 pathologic lesions could be evaluated. MRI was superior in the detection of suspect metastases compared to conventional radiography and scintigraphy (P less than 0.0001 and p less than 0.01, respectively). MRI also gave useful information about adjacent soft tissue components, vessels, nerves and spinal cord compression, i.e. useful information when planning stabilizing surgery. Both MRI and CT were sensitive and specific methods but when comparing 120 pathologic lesions the detection rate of MRI was significantly higher than that of CT (p less than 0.01). In conclusion, scintigraphy and conventional radiography are adequate enough if palliative radiotherapy is planned. When considering surgery MRI is advocated preoperatively for defining operability.