The aim of this study was to evaluate the use of computerized cuff pressure algometry (CPA) in fibromyalgia (FM) and to correlate deep-tissue sensitivity assessed by CPA with other disease markers of FM. Forty-eight women with FM and 16 healthy age-matched women were included. A computer-controlled, pneumatic tourniquet cuff was placed over the gastrocnemius muscle. The cuff was inflated, and the subject rated the pain intensity continuously on an electronic Visual Analogue Scale (VAS). The subject stopped the inflation at the pressure-pain tolerance and the corresponding VAS-score was determined (pressure-pain limit). The pressure at which VAS firstly exceeded 0 was defined as the pressure-pain threshold. Other disease markers (FM only): Isokinetic knee muscle strength, tenderpoint-count, myalgic score, Beck Depression Inventory, and Fibromyalgia Impact Questionnaire. Student's T-test was used to compare pressure-pain threshold and pressure-pain tolerance and the Mann-Whitney test to compare pressure-pain limit. Pearson's correlation was used to detect linear relationships. Pressure-pain threshold and pressure-pain tolerance assessed by CPA were significantly lower in FM compared to healthy controls. There was no difference in pressure-pain limit. CPA-parameters were significantly correlated to isokinetic muscle strength where more hypersensitivity resulted in lower strength. Pressure-pain threshold and pressure-pain tolerance assessed by CPA were significantly lower in patients with FM indicating muscle hyperalgesia. CPA was associated with knee muscle strength but not with measures thought to be influenced by psychological distress and mood.

UNLABELLED: Dissolution of the inorganic phase of bone by the osteoclasts mediated by V-ATPase and ClC-7 is a prerequisite for bone resorption. Inhibitors of osteoclastic V-ATPase or ClC-7 are novel approaches for inhibition of osteoclastic bone resorption. By testing natural compounds in acidification assays, diphyllin was identified. We characterized diphyllin with respect to the pharmacological effects on osteoclasts.

INTRODUCTION: Osteoclastic acidification of the resorption lacuna and bone resorption requires activity of both V-ATPase and the chloride channel ClC-7. Inhibition of these processes represents a novel approach for treatment of bone metabolic disorders. We identified diphyllin, a novel inhibitor of V-ATPase, and characterized this natural compound with respect to activity in human osteoclasts.

MATERIALS AND METHODS: Diphyllin was tested in the acid influx assay and V-ATPase assay using bovine chromaffin granules. Human osteoclasts were generated from CD14+ monocytes cultured with macrophage-colony stimulating factor (M-CSF) and RANKL. The effect of diphyllin on lysosomal acidification in human osteoclasts was studied using acridine orange. The effect of diphyllin on bone resorption by osteoclasts was measured as release of C-terminal cross-linked telopeptide of type I collagen (CTX-I) and calcium into the supernatants and by scoring pit area. Osteoclast number, TRACP activity, and cell viability were measured. Furthermore, the effect of diphyllin on bone nodule formation was tested using the mouse osteoblast cell line MC3T3-E1.

RESULTS: In the acid influx assay, diphyllin potently inhibited the acid influx (IC50 = 0.6 nM). We found that diphyllin inhibited V-ATPase with an IC50 value of 17 nM, compared with 4 nM for bafilomycin A1. Moreover, diphyllin dose-dependently inhibited lysosomal acidification in human osteoclasts. Furthermore, we found that diphyllin inhibited human osteoclastic bone resorption measured by CTX-I (IC50 = 14 nM), calcium release, and pit area, despite increasing TRACP activity, numbers of osteoclasts, and cell viability. Finally, diphyllin showed no effect on bone formation in vitro, whereas bafilomycin A1 was toxic.

CONCLUSIONS: We identified a natural compound that potently inhibits V-ATPase and thereby lysosomal acidification in osteoclasts, which leads to abrogation of bone resorption. Because recent studies indicate that inhibition of the osteoclastic acidification leads to inhibition of resorption without inhibiting formation, we speculate that diphyllin is a potential novel treatment for bone disorders involving excessive resorption.

Impairment of the dynamic control of the lumbopelvic complex in LBP has gained increased focus both clinically and experimentally. The objectives of this study were to determine the reliability of inclinometry as a measure of dynamic lumbopelvic control. Lumbopelvic reposition accuracy during pelvic tilts was measured in 39 healthy subjects using an inclinometer attached to the skin at S2 level. The reposition accuracy was measured in sitting, standing and supported standing. Tests were performed three times with a 20 min recess between tests. Only data from the last two test sequences were used in order to account for learning effects. Intraclass correlation coefficients were low for the sitting (0.54) and supported standing positions (0.36). In the standing position, a significant difference between test and retest was observed (P = 0.003) and further reliability analysis was therefore abandoned. It is concluded that inclinometry is not reliable for measuring the dynamic lumbopelvic control in any of the test positions and prior work utilising inclinometry to evaluate dynamic lumbopelvic control should be interpreted with caution.

Pain is a cardinal symptom in musculoskeletal diseases involving the knee joint, and aberrant movement patterns and motor control strategies are often present in these patients. However, the underlying neuromuscular mechanisms linking pain to movement and motor control are unclear. To investigate the functional significance of muscle pain on knee joint control during walking, three-dimensional gait analyses were performed before, during, and after experimentally induced muscle pain by means of intramuscular injections of hypertonic saline (5.8%) into vastus medialis (VM) muscle of 20 healthy subjects. Isotonic saline (0.9%) was used as control. Surface electromyography (EMG) recordings of VM, vastus lateralis (VL), biceps femoris, and semitendinosus muscles were synchronized with the gait analyses. During experimental muscle pain, the loading response phase peak knee extensor moments were attenuated, and EMG activity in the VM and VL muscles was reduced. Compressive forces, adduction moments, knee joint kinematics, and hamstring EMG activity were unaffected by pain. Interestingly, the observed changes persisted when the pain had vanished. The results demonstrate that muscle pain modulated the function of the quadriceps muscle, resulting in impaired knee joint control and joint instability during walking. The changes are similar to those observed in patients with knee pain. The loss of joint control during and after pain may leave the knee joint prone to injury and potentially participate in the chronicity of musculoskeletal problems, and it may have clinically important implications for rehabilitation and training of patients with knee pain of musculoskeletal origin.

OBJECTIVE: To analyze whether fibromyalgia (FM) and FM-like symptoms are related to an increased incidence of cancer.

METHODS: We identified 1361 patients referred on suspicion of FM in the period 1984-99 from hospital records. Following the American College of Rheumatology (ACR) criteria, patients were divided into subgroups with and without confirmed FM. The cohort was followed to the end of 1999 and linked to the files of the Danish Cancer Register. Site-specific standardized incidence ratios (SIR) were calculated.

RESULTS: We found no association between FM and cancer in 1132 female patients with confirmed FM at our institution (SIR 1.2, 95% CI 0.8-1.8). In 106 women referred for muscle pain and/or tenderness who did not meet the criteria for FM, an increased overall SIR was observed (SIR 2.5, 95% CI 1.2-4.6), with increased risk for breast cancer (SIR 4.8, 95% CI 1.6-11.3) and lymphatic and hematological cancers (SIR 10.6, 95% CI 1.2-38.2). There were 4 lung cancers in 84 men with confirmed FM (SIR 12.6, 95% CI 3.4-32.4).

CONCLUSION: Neither confirmed FM nor those without confirmed FM predicted cancer. An increased risk of breast cancer was found among those who did not meet the ACR criteria for FM. These patients should be investigated if they develop any new or warning symptoms of malignancy, and treating physicians should be vigilant with screening procedures such as mammography.