Assessment of functional respiratory complaints and related factors in people with hypermobile Ehlers-Danlos syndrome: Cross-sectional study.

BACKGROUND: Hypermobile Ehlers-Danlos Syndrome (hEDS) is the most common type of EDS. Apart from joint symptoms, people with hEDS have systemic manifestations as a chronic modification of the breathing pattern (functional respiratory complaints (FRCs)) and mental disorders. However, the prevalence of FRCs, and its relationship with mental disorders, have not yet been estimated for this population. OBJECTIVES: To assess the FRCs, central sensitization, disease perception, depression, and anxiety in people with hEDS from Belgium; and to identify the clustering of FRCs and determine any association with the characteristics assessed for this sample. METHODS: This cross-sectional study assessed socio-demographic characteristics, Nijmegen questionnaire (NQ), Central Sensitization Inventory (CSI), Brief Illness Perception Questionnaire, and the Hospital Anxiety and Depression Scale (HADS) in people with hEDS from Belgium. A two-step cluster analysis was performed to identify clusters according to NQ, and to understand how the other questionnaires are grouped among these clusters. RESULTS: The Spearman correlation coefficients showed that all the outcomes were significantly and positively correlated with each other (p<0.05). Furthermore, 84.9% of the sample had symptoms suggestive of FRCs, and 54.3% had probable anxiety. Three clusters were grouped (no FRCs, mild FRCs, and severe FRCs), with NQ, HADS-D and CSI-part A being the variables that contributed the most. People from cluster of severe FRCs got the worst scores for all the questionnaires. CONCLUSION: FRCs, central sensitization, depression, and anxiety are prevalent comorbidities in people with hEDS. Moreover, those people with FRCs had worse results in the investigated parameters, with depression being the variable that contributed the most to the clusters of FRCs. Consequently, investigating mechanisms for these co-occurring symptom profiles may improve our understanding of pathogenesis and indicate new management strategies to alleviate these symptoms and lead to the development of more effective care for persons with hEDS.

Gender-Related Impact of Sclerostin Antibody on Bone in the Osteogenesis Imperfecta Mouse.

Osteogenesis imperfecta (OI), which is most often due to a collagen type 1 gene mutation, is characterized by low bone density and bone fragility. In OI patients, gender-related differences were reported, but data in the literature are not convergent. We previously observed that sclerostin antibody (Scl-Ab), which stimulates osteoblast Wnt pathway via sclerostin inactivation, improved spine and long-bone parameters and biomechanical strength in female oim/oim mice, a validated model of human type 3 OI. Here, we wanted to highlight the effect of Scl-Ab on male oim/oim bones in order to identify a possible distinct therapeutic effect from that observed in females. According to the same protocol as our previous study with female mice, male wild-type (Wt) and oim/oim mice received vehicle or Scl-Ab from 5 to 14 weeks of age. Clinimetric and quantitative bone parameters were studied using X-rays, peripheral quantitative computed tomography, microradiography, and dynamic histomorphometry and compared to those of females. Contrary to Wt mice, male oim/oim had significantly lower weight, snout-sacrum length, and bone mineral content than females at 5 weeks. No significant difference in these clinimetric parameters was observed at 14 weeks, whereas male oim showed significantly more long-bone fractures than females. Scl-Ab improved bone mineral density and bone volume/total volume ratio (BV/TV) of vertebral body in Wt and oim/oim, without significant difference between male and female at 14 weeks. Male vehicle oim/oim had a significantly lower cortical thickness (Ct.Th) and BV/TV of tibial diaphysis than female and showed a higher number of fractures at 14 weeks. Scl-Ab increased midshaft periosteal apposition rate in such a way that tibial Ct.Th of male oim/oim was not significantly different from the female one at 14 weeks. The number of fractures was lower in male than female oim/oim after 14 weeks of Scl-Ab treatment, but this difference was not significant. Nevertheless, Scl-Ab-treated oim/oim male and female mice remained smaller than the Wt ones. In conclusion, our results highlighted differences between male and female oim/oim at 4 and 14 weeks of age, as well as some male-specific response of cortical bone to Scl-Ab. These gender-related particularities of oim/oim should be considered when testing experimental treatments.

Sclerostin-Antibody Treatment Decreases Fracture Rates in Axial Skeleton and Improves the Skeletal Phenotype in Growing oim/oim Mice.

In osteogenesis imperfecta (OI), vertebrae brittleness causes thorax deformations and leads to cardiopulmonary failure. As sclerostin-neutralizing antibodies increase bone mass and strength in animal models of osteoporosis, their administration in two murine models of severe OI enhanced the strength of vertebrae in growing female Crtap-/- mice but not in growing male Col1a1Jrt/+ mice. However, these two studies ignored the impact of antibodies on spine growth, fracture rates, and compressive mechanical properties. Here, we conducted a randomized controlled trial in oim/oim mice, an established model of human severe OI type III due to a mutation in Col1a2. Five-week-old female WT and oim/oim mice received either PBS or sclerostin antibody (Scl-Ab) for 9 weeks. Analyses included radiography, histomorphometry, pQCT, microcomputed tomography, and biomechanical testing. Though it did not modify vertebral axial growth, Scl-Ab treatment markedly reduced the fracture prevalence in the pelvis and caudal vertebrae, enhanced osteoblast activity (L4), increased cervico-sacral spine BMD, and improved the lumbosacral spine bone cross-sectional area. Scl-Ab did not impact vertebral height and body size but enhanced the cortical thickness and trabecular bone volume significantly in the two Scl-Ab groups. At lumbar vertebrae and tibial metaphysis, the absolute increase in cortical and trabecular bone mass was higher in Scl-Ab WT than in Scl-Ab oim/oim. The effects on trabecular bone mass were mainly due to changes in trabecular number at vertebrae and in trabecular thickness at metaphyses. Additionally, Scl-Ab did not restore a standard trabecular network, but improved bone compressive ultimate load with more robust effects at vertebrae than at metaphysis. Overall, Scl-Ab treatment may be beneficial for reducing vertebral fractures and spine deformities in patients with severe OI.

Sclerostin antibody reduces long bone fractures in the oim/oim model of osteogenesis imperfecta.

Osteogenesis imperfecta type III (OI) is a serious genetic condition with poor bone quality and a high fracture rate in children. In a previous study, it was shown that a monoclonal antibody neutralizing sclerostin (Scl-Ab) increases strength and vertebral bone mass while reducing the number of axial fractures in oim/oim, a mouse model of OI type III. Here, we analyze the impact of Scl-Ab on long bones in OI mice. After 9 weeks of treatment, Scl-Ab significantly reduced long bone fractures (3.6 ±â€¯0.3 versus 2.1 ±â€¯0.8 per mouse, p < 0.001). In addition, the cortical thickness of the tibial midshaft was increased (+42%, p < 0.001), as well as BMD (+28%, p < 0.001), ultimate load (+86%, p < 0.05), plastic energy (+184%; p < 0.05) and stiffness (+172%; p < 0.01) in OI Scl-Ab mice compared to OI vehicle controls. Similar effects of Scl-Ab were observed in Wild type (Wt) mice. The plastic energy, which reflects the fragility of the tissue, was lower in the OI than in the Wt and significantly improved with the Scl-Ab treatment. At the tissue level by nanoindentation, Scl-Ab slightly increased the elastic modulus in bones of both OI and Wt, while moderately increasing tissue hardness (+13% compared to the vehicle; p < 0.05) in Wt bones, but not in OI bones. Although it did not change the properties of the OI bone matrix material, Scl-Ab reduced the fracture rate of the long bones by improving its bone mass, density, geometry, and biomechanical strength. These results suggest that Scl-Ab can reduce long-bone fractures in patients with OI.

Inspiratory muscle strength training improves lung function in patients with the hypermobile Ehlers-Danlos syndrome: A randomized controlled trial.

As exertional inspiratory dyspnea is a common disabling complaint in hypermobile Ehlers-Danlos syndrome (hEDS) often also known as joint hypermobility syndrome (JHS), we investigated inspiratory muscle (IM) strength in patients with hEDS, and we assessed the effects of IM training (IMT) on IM strength, lung function, and exercise capacity. A prospective evaluation of IM strength followed by a randomized controlled trial of IMT was performed in women with hEDS. Sniff nasal inspiratory pressure (SNIP) was used to routinely measure IM strength and IMT was carried out using a pressure threshold device. IM strength (main outcome), cardiopulmonary function, exercise capacity, and emotional distress of both the treated and control groups were evaluated at the start and at the end of the 6-week training period. IM strength was reduced (<80% of predicted) in 77% of patients (80/104). Lung function was normal, although 24% of patients had a higher forced expiratory vital capacity (FVC) than normal and 12% of patients had a higher total lung capacity (TLC) than normal. Both the IMT and control groups (n = 20) had similar baseline characteristics. Significant changes were noted only in the IMT group after IMT. At the end of the program, IMT improved SNIP (20%) (before: 41 ± 17 cm H2 O [28, 53] vs. after: 49 ± 18 cm H2 O [34;65]), six-minute walking distance (6MWD) (60 m) (455 ± 107 m [379,532] vs. 515 ± 127 m [408, 621]), and forced expiratory volume in one second (FEV1) (285 mL) (94 ± 14% pred [84,104] vs. 103 ± 11% pred [94, 112]). IM strength is significantly reduced in patients with hEDS. IMT improved IM strength, lung function, and exercise capacity. Our findings suggest that IMT should be added to usual care.

CT arthrography of adhesive capsulitis of the shoulder: Are MR signs applicable?

OBJECTIVE: To determine if diagnostic signs of adhesive capsulitis (AC) of the shoulder at Magnetic Resonance Imaging (MRI) and arthrography (MRA) are applicable to CT arthrography (CTA). METHODS: 22 shoulder CTAs with AC were retrospectively reviewed for features described in MR literature. The control group was composed of 83 shoulder CTA divided into four subgroups 1) normal (N = 20), 2) omarthrosis (N = 19), 3) labral injury (N = 23), and 4) rotator cuff tear (N = 21). Two musculoskeletal radiologists assessed the rotator interval (RI) for obliteration, increased width and thickening of coracohumeral ligament (CHL). The width and capsule thickness of the axillary recess were measured. RESULTS: The width of the axillary recess was significantly decreased in the AC group (4.6 ± 2.6 mm versus 9.9 ± 4.6 mm, p ≤ 0.0001; sensitivity and specificity of 84% and 80%). Thickness of the medial and lateral walls of the axillary capsule was significantly increased in the AC group (5.9 ± 1.3 mm versus 3.7 ± 1.1 mm, p ≤ 0.0001 and 5.7 ± 1 mm versus 3.5 ± 1.3 mm, p ≤ 0.0001, respectively). CHL thickness was significantly increased in the AC group (4.1 ± 1 mm (p ≤ 0.001)) in comparison to others groups. Obliteration of the RI was statistically significantly more frequent in patients with AC (72.7% (16/22) vs. 12% (10/83), p < 0.0001). Width of the RI did not differ significantly between patients and controls (p ≥ 0.428). CONCLUSION: Decreased axillary width, and thickened axillary capsule are MR signs of AC applicable to CTA. Evaluation of rotator interval seems useful and reproducible only for obliteration.

Dermal ultrastructure in low Beighton score members of 17 families with hypermobile-type Ehlers-Danlos syndrome.

The distinction between the Ehlers-Danlos syndrome hypermobile type (EDSH) and the benign joint hypermobility syndrome (BJHS) is unclear. The aim of the present study was to compare skin ultrastructural abnormalities of EDSH and BJHS among different families. Skin of 23 EDSH, 27 BJHS, and 41 asymptomatic subjects from 17 families was examined using transmission electron microscopy. Similar ultrastructural abnormalities were found irrespective of the Beighton score. Flower-like collagen fibrils represented the key change and elastic fibers were altered as well. Beighton score is a clinical parameter rating joint mobility that appeared unrelated to quantitative and qualitative collagen ultrastructural alterations in the skin. Some EDSH family members fit with BJHS diagnosis. BJHS possibly represents a mild variant of EDSH.

Is there a place for bone turnover markers in the assessment of osteoporosis and its treatment?

As populations age, the number of osteoporotic fractures will increase. Bone mineral density (BMD) measurement remains the major way to diagnose osteoporosis and to indicate therapy. The FRAX tool, based on clinical risk factors, estimates the 10-year risk of hip and major osteoporotic fractures. The association of BMD and FRAX measurements has improved the identification of patients who are most at risk. However, some patients can still be overlooked and denied therapy. It is sound that adding the measure of bone turnover markers to the former risk factors and their follow-up during therapy could best address the efficacy of treatment of osteoporosis. Whether this behavior is cost-effective remains to be settled.

Biologicals in osteoporosis: teriparatide and parathyroid hormone in women and men.

Osteoporosis is characterized by the occurrence of a host of fractures. According to densitometric values, an operational definition for osteoporosis corresponds to a loss of 25% to 30% (-2.5 T-scores) compared with the mean values of bone mineral density of young premenopausal women. For years, research tried to develop drugs to improve the bone mineral density. According to the compounds, antiresorptive agents are able to decrease the fracture rate by about 30% to 70%, and to increase the bone mineral density. However, the agents increasing the most bone mineral density are not necessarily those that influence the most fracture rates. It has been known for years that parathyroid hormone (PTH) administered cyclically is able to increase bone mineral density. Two analogues of PTH have been developed: PTH (1-34) and PTH (1-84). Both of them are able to increase bone mineral density and reduce the rate of vertebral fracture but not of the hip, nor of nonvertebral fractures, the latter at least for PTH (1-84). Their exact place in the armamentarium of therapy of osteoporosis and their best time of administration are not yet definitely settled. New modes of administration (transdermal, intranasal, oral) will probably become available soon. With all the drugs available today and those still in development, it can be hoped that osteoporosis will become a disease of the past.

Urban tropospheric ozone increases the prevalence of vitamin D deficiency among Belgian postmenopausal women with outdoor activities during summer.

CONTEXT: By absorbing sunlight UVB and thereby reducing cutaneous vitamin D photosynthesis, ozone, a common urban pollutant, could cause hypovitaminosis D. OBJECTIVES: The objective of the study was to establish the characteristics and percentage of subjects with serum 25-hydroxyvitamin D [25(OH)D] less than 75 nmol/liter among postmenopausal women engaging in outdoor activities in either Brussels or the countryside. DESIGN/SETTING: This was a cross-sectional study conducted in a university research hospital. PATIENTS/METHODS: Among 249 women consulting for either shoulder tendonitis or lumbar spine osteoarthritis, 121 free of conditions and drugs affecting bone and calcium metabolism completed two food-frequency questionnaires within 15 d and we selected the 85 subjects with retest scores within the +/- 15% of test scores. Other parameters included sun exposure index (SEI), PTH levels, and femoral neck T-score. RESULTS: Urban residents (n = 38) and rural residents (n = 47) did not differ in mean ages, body mass indices, and vitamin D intakes. When compared with rural inhabitants, urban inhabitants were exposed to ozone levels 3 times higher, and despite a higher mean SEI (113 vs. 87; P < 0.001), they had a higher prevalence of 25(OH)D less than 75 nmol/liter (84 vs. 38%). After adjusting for SEI, 25(OH)D was 2-fold higher in rural residents, and after adjusting for 25(OH)D, SEI was 3-fold higher in urban residents. Femoral neck T-scores correlated positively with 25(OH)D and negatively with PTH levels. CONCLUSIONS: Air pollution may be a neglected risk factor for hypovitaminosis D, which is known to compromise several health outcomes. As long as 25(OH)D is greater than 75 nmol/liter, calcium intakes greater than 17.5 mmol/d are unnecessary to prevent elevations in PTH levels.

Zoledronic acid for treatment of Paget's disease of bone.

Paget's disease of bone is characterised by a focal increase in bone resorption and bone formation. This anarchic metabolism leads to disorganised bone, with bone pain, fragility, deformity and compression of the peripheral or CNS according to the involved site. Quality of life of sufferers is dramatically impaired. Symptomatic therapy trends to relieve pain, but cannot seek to prevent other complications. Only 'specific' therapy can fulfil this purpose. Bisphosphonates have become the cornerstone for therapy of Paget's disease in the last 25 years. Progressively stronger bisphosphonates have been launched on the market. The last drug available, zoledronic acid, the most potent of this drug family, can be administered intravenously. It possesses a long-acting efficacy, allowing a follow up on a yearly basis and permitting the chance of a very long remission of the Pagetic lesion. In the long term, prevention of severe complications can be envisaged, with a reasonable pharmacoeconomic cost.

Oral salmon calcitonin reduces Lequesne's algofunctional index scores and decreases urinary and serum levels of biomarkers of joint metabolism in knee osteoarthritis.

OBJECTIVE: To evaluate the effects of oral salmon calcitonin (sCT) on Lequesne's algofunctional index scores and on biomarkers of joint metabolism in knee osteoarthritis. METHODS: In this randomized, double-blind trial, patients received either placebo (n = 18), 0.5 mg of sCT (n = 17), or 1 mg of sCT (n = 18) daily for 84 days. Biomarkers included C-telopeptide of type II collagen (CTX-II), type II collagen neoepitope C2C, collagenases (matrix metalloproteinase 1 [MMP-1], MMP-8, and MMP-13), stromelysin (MMP-3), tissue inhibitors of metalloproteinases 1 and 2, and hyaluronan. Statistical analysis included nonparametric tests. RESULTS: A total of 41 patients completed the study (13 in the group receiving 0.5 mg of sCT and 14 in each of the other 2 other groups). Although, on day 84, patients in both the placebo group and the group receiving 1 mg of sCT exhibited a similar significant decrease in pain scores, a significant reduction in the function score was observed only in the 2 sCT groups. On day 84, there was no significant decrease in biomarker levels in the placebo group, whereas significant reductions in the levels of both MMP-3 and hyaluronan were observed in the 2 sCT groups. The group of patients receiving 1 mg of sCT exhibited significant decreases in the levels of CTX-II, C2C, and MMP-13. CONCLUSION: By improving functional disability and by reducing levels of biomarkers that are thought to be predictive of joint space narrowing (and thus cartilage loss), oral sCT at a dose of 1 mg might be a useful pharmacologic agent in human knee OA.

Inulin and fructo-oligosaccharides differ in their ability to enhance the density of cancellous and cortical bone in the axial and peripheral skeleton of growing rats.

Although dietary fructans improve calcium absorption and bone mineral content (BMC) in rats, their effect on calcium bioavailability and bone density may vary with their degree of polymerization. Therefore, for a 3-month period, growing rats received either a control diet or a diet enriched with either oligofructose (OLF) or inulin. At sacrifice, body weight, lean body mass and appendicular bone length were similar in the 3 groups. Rats fed fructans had a similar increase in cecal wall weight (30%), but the relative increase in cecal levels of calbinding-9 K was 2 in the OLF group and 4 in the inulin group. Further, the significant decrease in serum levels of type I collagen C-telopeptide was greater in the inulin group (30%) than in the OLF group (16%). The increase in whole-body bone mineral content (BMC) as measured by DXA was greater in the inulin group than in the OLF group but DXA detected an increase in the BMC of excised femurs only in the inulin group. In contrast, pQCT conducted ex vivo detected a significant increase in the area and mineral density (BMD) of the cancellous bone of both the proximal tibia and vertebra in rats fed fructans and the effect of inulin was greater (P < 0.01) than that of OLF (P < 0.05). Further, inulin but not OLF significantly enhanced the BMD of the cortical bone in both appendicular and peripheral sites (P < 0.01) as well as the polar stress/strain index of femurs (P < 0.01). These observations suggest that, although both inulin and OLF both have a positive effect on BMD, the greatest effect of inulin is related to the higher capacity of this fructan to reduce bone resorption. The different anti-resorptive capacity of the 2 fructans might be related to their different impact on calcium absorption and bioavailability since the increase in cecal amounts of calbindin-9 K, a protein known to play an important role in calcium absorption, was greater in rat fed inulin than in rats fed OLF. Although cecal wall hyperplasia may be of concern, it remains to establish whether the positive effect of fructans observed on calcium absorption in humans is also associated with a positive effect on bone mass and/or mineral density.

Comparative effect of nimesulide and ibuprofen on the urinary levels of collagen type II C-telopeptide degradation products and on the serum levels of hyaluronan and matrix metalloproteinases-3 and -13 in patients with flare-up of osteoarthritis.

BACKGROUND AND AIM: Because in vitro studies have shown that nimesulide not only preferentially inhibits COX-2 but also reduces the action/release of pro-inflammatory cytokines, down-regulates the synthesis and/or activity of collagenase(s), and releases reactive oxygen species and other toxic substances from neutrophils, this study investigated whether nimesulide and ibuprofen could affect levels of biochemical markers of joint inflammation and collagen catabolism in patients with flare-up of knee or hip osteoarthritis. METHODS: Ninety patients were included in this randomised, prospective, single- blind study. They received either nimesulide (n = 45) or ibuprofen (n = 45) for a 4-week treatment period. The following parameters were analysed by ELISA: urinary levels of C-terminal cross-linking telopeptide of type II collagen (CTX-II), a marker of type II collagen breakdown; serum levels of hyaluronan (HA), a marker of synovial inflammation and hyperplasia; and circulating levels of stromelysin-1 (matrix metalloproteinase-3 [MMP-3]), collagenase-1 (MMP-1) and collagenase-3 (MMP-13). Statistical analysis used was ANOVA. RESULTS: At the end of the treatment period, nimesulide but not ibuprofen markedly reduced the urinary levels of CTX-II (p < 0.001) and the serum levels of HA (p < 0.05), two markers known to prognosticate poor outcome of the osteoarthritis disease process. Nimesulide also reduced the serum levels of both MMP-3 (p < 0.05) and MMP-13 (p < 0.001). Furthermore, in the nimesulide group, the decrease in levels of CTX-II correlated significantly with the decrease in levels of HA and MMP-13. CONCLUSION: Although nonsteroidal anti-inflammatory drugs are effective in improving pain and disability in OA patients, to date it has been unclear to what extent these drugs could affect joint metabolism and hence joint structure. Patients with flare-up of their osteoarthritis disease process exhibit enhanced levels of markers of joint inflammation and cartilage collagen breakdown, which were markedly decreased by nimesulide but not by ibuprofen.

Chondrocytes, synoviocytes and dermal fibroblasts all express PH-20, a hyaluronidase active at neutral pH.

Hyaluronan (HA), an important component of connective tissues, is highly metabolically active, but the mechanisms involved in its catabolism are still largely unknown. We hypothesized that a protein similar to sperm PH-20, the only mammalian hyaluronidase known to be active at neutral pH, could be expressed in connective tissue cells. An mRNA transcript similar to that of PH-20 was found in chondrocytes, synoviocytes, and dermal fibroblasts, and its levels were enhanced upon stimulation with IL-1. In cell layers extracted with Triton X-100 - but not with octylglucoside - and in culture media, a polyclonal antipeptide anti-PH-20 antibody identified protein bands with a molecular weight similar to that of sperm PH-20 (60 to 65 kDa) and exhibiting a hyaluronidase activity at neutral pH. Further, upon stimulation with IL-1, the amounts of the neutral-active hyaluronidase increased in both cell layers and culture media. These findings contribute potential important new insights into the biology of connective tissues. It is likely that PH-20 facilitates cell-receptor-mediated uptake of HA, while overexpression or uncontrolled expression of the enzyme can cause great havoc to connective tissues: not only does HA fragmentation compromise the structural integrity of tissues, but also the HA fragments generated are highly angiogenic and are potent inducers of proinflammatory cytokines. On the other hand, the enzyme activity may account for the progressive depletion of HA seen in osteoarthritis cartilage, a depletion that is believed to play an important role in the apparent irreversibility of this disease process.

Role of alendronate in therapy for posttraumatic complex regional pain syndrome type I of the lower extremity.

OBJECTIVE: To evaluate the effects of the antiresorptive agent alendronate at a daily oral dose of 40 mg in patients with posttraumatic complex regional pain syndrome type I (CRPS I) of the lower extremity. METHODS: Forty patients were enrolled in this 8-week randomized, double-blind, placebo-controlled study of alendronate therapy for CRPS I, a condition associated with regional osteoclastic overactivity. An optional 8-week open extension of alendronate therapy (weeks 12-20) was available after a 4-week period without therapy. Clinical assessments included joint mobility, edema of the lower extremity, tolerance to pressure in the lower extremity, and levels of spontaneous pain. Urinary levels of type I collagen N-telopeptide (NTX) were assessed by enzyme-linked immunosorbent assay. Patients were examined at weeks 4, 8, 12, 16, 20, and 24. Statistical analysis included two-way factorial analysis of variance. RESULTS: In contrast to placebo-treated patients (n = 20), all of the alendronate-treated patients (n = 19) exhibited a marked and sustained improvement in levels of spontaneous pain, pressure tolerance, and joint mobility, as well as a significant reduction in urinary levels of NTX at weeks 4 and 8. The improvement was maintained at week 12. Twelve patients from each treatment group volunteered for the 8-week open trial, and all of them had a positive response to alendronate. CONCLUSION: Our findings support the use of oral alendronate in posttraumatic CRPS I. By reducing local acceleration of bone remodeling, alendronate might relieve pain by effects on nociceptive primary afferents in bone, pain-associated changes in the spinal cord, and possibly also through a central mechanism.

Treatment with calcitonin prevents the net loss of collagen, hyaluronan and proteoglycan aggregates from cartilage in the early stages of canine experimental osteoarthritis.

OBJECTIVE: To evaluate the effect of calcitonin (CT) on the histology and biochemistry of articular cartilage from unstable operated and nonoperated knee in a canine model of experimental osteoarthritis (OA). METHODS: Eighteen dogs underwent anterior cruciate ligament transection (ACLT) of the right knee and were randomly distributed into three groups of six dogs each. From day-1 after surgery until sacrifice 84 days post-ACLT, each dog received a daily nasal spray that delivered the placebo, 100 units of CT or 400 units of CT. Histologic lesions were scored. Hyaluronan (HA) and antigenic keratan sulfate (AgKS) were quantified by enzyme-linked immunosorbent assays (ELISAs), whereas aggrecan molecules extracted under nondissociative conditions were characterized by velocity gradient centrifugation. RESULTS: All canine cruciate-deficient knees developed OA. At a daily dose of 400 units, CT had no effect on the size of osteophytes but significantly reduced the severity of cartilage histologic lesions in unstable knees. CT also enhanced the HA content as well as the size distribution and relative abundance of fast-sedimenting aggrecan aggregates in cartilage from both operated and nonoperated knees. On the other hand, in the CT-treated group, the cartilage content of AgKS increased in operated joints, but not in nonoperated joints. CONCLUSIONS: Because CT delivered as a nasal spray markedly reduced the severity of most OA changes, both at the histological and biochemical level, this form of therapy may have benefits for humans who have recently experienced a traumatic knee injury, and as well as for dogs who spontaneously rupture their ACL.

Effects of calcitonin on subchondral trabecular bone changes and on osteoarthritic cartilage lesions after acute anterior cruciate ligament deficiency.

UNLABELLED: Because SBM may contribute to cartilage breakdown in OA, experimental OA was induced in dogs by transecting the anterior cruciate ligament of the knee and treating with either CT or a placebo. CT significantly reduced both SBM and cartilage lesions. This study supports the use of CT in the treatment of canine experimental OA. INTRODUCTION: Because subchondral bone remodeling (SBM) may contribute to cartilage breakdown in osteoarthritis (OA), we evaluated to what extend calcitonin (CT) might affect cartilage and bone changes in the early stages of canine experimental OA. MATERIALS AND METHODS: Twelve dogs underwent transection of the anterior cruciate ligament (ACLT) of the right knee. After ACLT, each animal received a daily nasal spray delivering either 400 U of CT (CT-treated group; n = 6) or a placebo (PL-treated group; n = 6). At day 84 after surgery, animals were killed, and cartilage changes were graded. BMD and volume fraction (BVF) were assessed by pQCT in different regions of interest (ROIs) of the subchondral cancellous bone of tibial plateaus (TPs). Statistics included a 2 x 2 factorial analysis with +/-CT as one factor and +/-ACLT as the other. RESULTS AND CONCLUSIONS: Nonoperated (N-OP) knees were normal in both groups. In the PL-treated group, ACLT knees all exhibited OA changes, which predominated in the medial knee compartment. Furthermore, compared with N-OP knees, the BMD and BVF of ACLT joints were both markedly reduced in medial TP but not in lateral TP. In contrast, in the CT-treated group, cartilage OA lesions of ACLT knees were significantly reduced, and there was no difference in BMD and BFV between N-OP and ACLT knees. These findings suggest that the loss of subchondral trabeculae contributes to cartilage breakdown, possibly by enhancing cartilage deformation on joint loading. By counteracting bone loss, CT reduced cartilage OA lesions, and thus, might be useful in the treatment of OA in cruciate-deficient dogs.