Effect of neridronate on axial involvement in patients with spondyloarthritis when biologics are not possible. Results of a monocentric study.

Introduction: This study aims to examine the potential effectiveness of intravenous neridronate (IVNer) on axial involvement in patients with spondyloarthritis (SpA) refractory to non-steroidal anti-inflammatory drugs (NSAIDs) but not eligible for biological disease-modifying antirheumatic drugs (bDMARDs). Method: Patients with active SpA (BASDAI score ≥ 4) and active sacroiliitis (SI) on MRI (according to ASAS MRI definition), who were NSAID-insufficient responder/intolerant but not eligible for bDMARDs, were retrospectively recruited in a tertiary rheumatology centre between September 2015 and December 2021. IVNer (100 mg) was administered to the patients on days 1, 4, 7, and 10. Responses were evaluated 60 days after the last infusion as the median changes from the baseline of BASDAI and Visual Analogue Scale (VAS) pain and there are improvements on MRI signs. Results: A total of 38 patients (26 axial SpA, 3 enteropathic arthritis, and 9 axial psoriatic arthritis) were included [66% women, mean age ± SD: 38.0 ± 14.1 years, mean disease duration: 30.5 ± 49.5 months (range 1.0-298), 47% HLAB27+]. The reason for bDMARD ineligibility was concurrent solid tumors (n = 6) or hematological (n = 1) malignancy, comorbidities (n = 11), or patient preference (n = 20). Both median BASDAI [5.83 (4.2-8.33) versus 3.66 (1.1-6.85), p < 0.001] and VAS pain [7 (5.75-8.0) versus 3 (1.0-7.0), p < 0.0001] significantly decreased after IVNer. Of 28 available MRI at follow-up, we observed a complete (36%) or partial (39%) resolution of sacroiliitis or a persistent activity (25%). Discussion: IVNer was effective in improving axial involvement in patients with SpA refractory to NSAIDs but not eligible for bDMARDs. IVNer can be considered as a potential alternative therapeutic option in selected settings.

Bone Involvement in Rheumatoid Arthritis and Spondyloartritis: An Updated Review.

Several rheumatologic diseases are primarily distinguished by their involvement of bone tissue, which not only serves as a mere target of the condition but often plays a pivotal role in its pathogenesis. This scenario is particularly prominent in chronic inflammatory arthritis such as rheumatoid arthritis (RA) and spondyloarthritis (SpA). Given the immunological and systemic nature of these diseases, in this review, we report an overview of the pathogenic mechanisms underlying specific bone involvement, focusing on the complex interactions that occur between bone tissue's own cells and the molecular and cellular actors of the immune system, a recent and fascinating field of interest defined as osteoimmunology. Specifically, we comprehensively elaborate on the distinct pathogenic mechanisms of bone erosion seen in both rheumatoid arthritis and spondyloarthritis, as well as the characteristic process of aberrant bone formation observed in spondyloarthritis. Lastly, chronic inflammatory arthritis leads to systemic bone involvement, resulting in systemic bone loss and consequent osteoporosis, along with increased skeletal fragility.

How the COVID-19 pandemic affected bone health: a retrospective, longitudinal study on denosumab persistence from the epicentre of European spreading.

In this study, we investigated how the COVID-19 pandemic involved osteoporosis care in patients treated with denosumab. Almost a third of patients missed the prescription renewal, mandatory to obtain the subsidized drug. Among patients who suspended denosumab, more than half reported fragility fractures. PURPOSE: This study aimed to evaluate persistence on denosumab (Dmab) treatment during the COVID-19 pandemic and the clinical effects of possible discontinuation. METHODS: We retrospectively assessed patients affected by osteoporosis and treated with Dmab, scheduled to have the yearly renewal of prescription between March 9, 2020, and May 9, 2021, 2 months after the second pandemic wave. In June 2022, a telephone survey started, by calling all patients who missed the yearly renewal of Dmab. Predictors of missed renewal and fragility fracture occurrence were assessed by logistic analyses. RESULTS: Patients scheduled to have a renewal of Dmab prescription during the observational period were 538 (age 75.5 ± 9.3 years, female 511). A total of 152 (28.2%) patients did not have the renewal. Patients not renewing Dmab prescription were significantly older (p = 0.01) and more frequently affected by pulmonary (p = 0.04) and cardiovascular comorbidity (p = 0.01). Telephone survey on non-persistent patients showed that 44 had died, 28 patients were missing, 23 shifted to bisphosphonate treatment, and 22 patients suspended Dmab. Following discontinuation, 12/22 patients (54.5%) reported fragility fractures; 5/22 had multiple fractures, for a total number of 18 fractures, mainly vertebral. Logistic analyses showed that the odds of Dmab withdrawal increased in older patients with pulmonary comorbidity and treated for a shorter time. Dmab discontinuation was the only variable that increased the risk of fracture. CONCLUSION: This study provided real-world data about an impaired persistence of Dmab treatment resulting in an increased number of fragility fractures in a geographic area heavily affected by the outbreak of COVID-19.

Long-term efficacy and safety of neridronate treatment in patients with complex regional pain syndrome type 1: a pre-specified, open-label, extension study.

Background: No data on the permanent and curative effect of bisphosphonate treatment in patients with complex regional pain syndrome type-1 (CRPS-1) are currently available. The aim of this pre-specified, open-label, observational study was to evaluate the long-term efficacy and safety of neridronate treatment. Design: A pre-specified, open-label, extension study. Methods: Patients treated with intramuscular (IM) placebo in the double-blind phase of the study were assigned to 100 mg intravenous (IV) neridronate treatment administered 4 times over 10 days. These patients, together with those previously treated with 400 mg IM neridronate, were followed for 1 year. Efficacy was assessed using a visual analogue scale (VAS) pain score. Changes in clinical signs and symptoms, quality of life (QoL) using the Short Form Health Survey (SF-36), and the McGill Pain Questionnaire were also assessed. Results: Benefits on pain, clinical and functional measures were maintained and further improved over 12 months in most patients treated with neridronate administered either IM or IV. In IM-treated patients, the percentage of those defined as responders (VAS score reduction ≥ 50%) progressively increased up to day 360 to 32 of 35 patients (91.4%). Among the 27 patients referred to as responders at the end of the double-blind phase, 26 reported the same result at day 360 (96.3%). In IV-treated patients, a responder rate of 88% (22 out 25) was found at day 360 (p = 0.66 between groups). Consistent improvements were also observed for all clinical signs and functional questionnaire. No drug-related adverse events were reported during the study. Conclusion: In patients with acute CRPS-1, the benefit in pain, clinical, and functional measures observed a few weeks after neridronate treatment administered either IM or IV is maintained and further improved over 12 months. Parenteral neridronate induces permanent disease remission preventing chronic pain and motor dysfunction. Trial registration: EU Clinical Trials Register (EudraCT Number): 2014-001156-28.

Persistence and recurrence in tumor-induced osteomalacia: A systematic review of the literature and results from a national survey/case series.

PURPOSE: Tumor induced osteomalacia (TIO) is a rare disease of mineral metabolism, whose clinical picture is dominated by hypophosphatemia usually due to an excess of circulating FGF23 produced by small mesenchymal tumors. Data on the real prevalence of the disease are lacking, with the knowledge of the disease mainly relying on case reports and small case series. No estimate is available on the prevalence of uncured TIO. METHODS: National multi-center, cross-sectional and retrospective study on persistent or recurrent cases of TIO followed in referral centers for bone diseases; systematic review of the published persistent and recurrent cases of TIO. Data from patients consecutively evaluated in referral Italian centers for bone diseases were collected; a PubMed search on persistent, recurrent and unoperable cases of TIO was carried out. RESULTS: Sixteen patients (mean age at diagnosis 52.5 ± 10.6 years) with persistent (n = 6, 37,5%), recurrent (n = 7, 43.7%) or not operable (n = 3, 18.8%) TIO were described. Delay in diagnosis (2.5 ± 1.3 years) was demonstrated. All patients experienced fragility fractures or pseudofractures and disabling bone and muscle pain. BMD was significantly reduced (mean T-score -2.7 ± 1.7 and -2.7 ± 0.9 at lumbar spine and femoral neck, respectively). Fourteen patients were maintained under therapy with phosphate salts and calcitriol, while in 2 patients therapy with burosumab, an anti-FGF23 antibody, was commenced. CONCLUSION: A significant number of patients with TIO remain either undiagnosed for tumor localization or tumor recur or persist after surgery. These patients with active disease represent possible candidates for burosumab treatment.

Intramuscular neridronate for the treatment of complex regional pain syndrome type 1: a randomized, double-blind, placebo-controlled study.

BACKGROUND: Complex regional pain syndrome type-1 (CRPS-1) is a severely disabling painful disease challenging to treat. This multicenter, randomized, double-blind placebo-controlled trial examined the efficacy of intramuscular (i.m.) neridronate in CRPS-1 patients. METHODS: A total of 78 patients diagnosed with CRPS-1 (aged 59.5 ± 10.3, 66.7% female) were randomly assigned to 25 mg (i.m.) neridronate (N = 41) given once daily for 16 consecutive days or placebo control (N = 37). Efficacy was assessed after 30 days using a visual analogue scale (VAS) pain score and the number of patients achieving ⩾50% reduction in VAS score. Change in clinical signs and symptoms, quality of life (QoL) using Short Form Health Survey (SF-36) and the McGill Pain Questionnaire were also assessed. RESULTS: After 30 days, VAS score decreased significantly to a greater extent in neridronate-treated patients versus placebo (31.9 ± 23.3 mm versus 52.3 ± 27.8 mm, p = 0.0003). Furthermore, the proportion of patients achieving a VAS reduction of ⩾50% was greater in the neridronate group (65.9% versus 29.7%, p = 0.0017). Clinical signs and symptoms were improved significantly in the neridronate group versus placebo for edema (72.5% versus 79.9%, p = 0.03), pain during motion (70% versus 83.3%, p = 0.0009), allodynia (20% versus 63.3%, p = 0.0004), and hyperalgesia (20% versus 56.7%, p = 0.0023). Whereas no difference was observed for QoL measures using the SF-36 questionnaire, three of the four pain variables using the McGill Pain Questionnaire improved significantly in the neridronate group. No serious drug-related adverse events were reported during the study. CONCLUSION: In patients with acute CRPS-1, i.m. injections of 25 mg neridronate were associated with clinically relevant benefit compared with placebo controls. TRIAL REGISTRATION: EU Clinical Trials Register: https://www.clinicaltrialsregister.eu/ctr-search/search?query=2014-001156-28.

Determinants of Diagnostic Delay in Complex Regional Pain Syndrome Type 1: An Observational Study of 180 Consecutive New Cases.

BACKGROUND/OBJECTIVE: Complex regional pain syndrome type 1 (CRPS-1) is a disabling painful disease, with variable outcomes in terms of chronic pain and disability. A long time between onset and diagnosis seems predictive for late recovery and progression toward a chronic disease. This study aims to investigate demographic and clinical variables associated with delayed CRPS-1 diagnosis. METHODS: From March 2013 to January 2018, consecutive patients newly diagnosed according to International Association for the Study of Pain diagnostic criteria for CRPS-1 were recruited. Demographic and clinical variables were collected at diagnosis. Student t test and Mann-Whitney U test were used for comparisons; Cox proportional hazards model was applied to evaluate the variables associated with delayed CRPS-1 diagnosis. RESULTS: One hundred eighty patients entered the study. At diagnosis, women were older, and foot was more often involved than hand. The triggering event was more commonly a trauma without fracture for foot disease and a fracture for hand localization. No differences between hand and foot disease were found by the International Association for the Study of Pain diagnostic categories (clinical vs research) or pain measures. Variables significantly associated with a longer time between disease onset and diagnosis were foot localization, general practitioner referral, higher number of visits before CRPS diagnosis, and prior physiotherapy prescribed for symptoms later diagnosed as CRPS. An overt clinical manifestation (research CRPS-1) predicted a shorter delay. CONCLUSIONS: Foot localization, prior physiotherapy prescribed for symptoms later diagnosed as CRPS, and a disease without overt clinical manifestations were independent predictive factors for a delayed diagnosis. Clinicians should pay attention to these issues to ensure a timely diagnosis and possibly avoid progression toward a chronic disease.

Bisphosphonates in the treatment of complex regional pain syndrome: is bone the main player at early stage of the disease?

Complex Regional Pain Syndrome type 1 (CRPS-1) is a disabling painful disease whose hallmark is pain disproportionate to inciting event. CRPS is also characterized by symptoms and signs, such as vasomotor, sudomotor, trophic and motor changes. Therapeutic approach of CRPS-1 still remains a challenge for clinicians treating a disease with potential heavy consequences on patient prognosis. In the past years, the treatment with bisphosphonates (BPs) has gained some success as confirmed by the results of a number of meta-analyses. The aim of this paper is to point out the pivotal role of bone in CRPS pathogenesis. The efficacy of BPs is likely to be related to bone tissue involvement in the early pathophysiological steps of the disease, as demonstrated by evidences highlighting the central role of bone in the initial phases. Bone can become a source of inflammatory cytokines when triggered by a direct injury. Moreover, peptidergic fibers that innervate both mineralized bone and bone marrow can play a role in triggering or maintaining the microvascular disturbance at bone level. Indeed, bone involvement is consistent with the mineralization disturbance as well as the results of instrumental investigations (e.g., MRI, bone scan). In this regard, an intriguing issue relies on the excellent therapeutic response to BPs treatment of other diseases (e.g., Transient Osteoporosis of the Hip and Regional Migratory Osteoporosis) that share with CRPS-1 some clinical and instrumental features.

Predictors of Responsiveness to Bisphosphonate Treatment in Patients with Complex Regional Pain Syndrome Type I: A Retrospective Chart Analysis.

Objective: The aim of this study was to assess whether the effectiveness of bisphosphonate infusion in patients with complex regional pain syndrome type I (CRPS-I) is influenced by variables related to patient and/or disease characteristics. Methods: This is a retrospective analysis of patients referred in the last five years to our rheumatologic tertiary care center, all fulfilling the Budapest CRPS-I diagnostic criteria and treated with three different bisphosphonate schedules (clodronate, pamidronate, and neridronate). For every subject, demographic and clinical variables were retrieved and retrospectively analyzed. We identified variables that independently influenced the therapeutic outcome of patients by a logistic regression analysis. For exploratory purposes, the effectiveness of the different bisphosphonate treatments employed was compared. Results: Among the 194 patients included in the analysis, the overall therapeutic response rate was 71.6%. Logistic regression analysis showed that the independent predictive variables for therapeutic effectiveness were disease duration (odds ratio [OR] = 0.83, 95% confidence interval [CI] = 0.72-0.96 for a one-month increment), fracture as a predisposing event (OR = 3.23, 95% CI = 1.29-8.03), and "warm" disease subtype (OR = 4.88, 95% CI = 1.57-15.20). These variables were found to influence the odds of responsiveness when analyzed together with age at onset, gender, and disease localization. No significant difference in therapeutic effectiveness was found by comparing the three different bisphosphonate schedules employed. Conclusion: Early disease, fracture as a predisposing event, and "warm" disease subtype are predictors of responsiveness to bisphosphonate treatment in patients with CRPS-I.

Algodystrophy: recent insight into the pathogenic framework.

Algodystrophy, nowadays called CRPS I, is a painful syndrome characterized by sensory and vasomotor disturbance, edema and functional impairment. Significant progress in knowledge about the pathogenic mechanisms of the disease have been recently achieved, but they are not yet fully understood and some clinical aspects are still lacking of a whole pathogenetic comprehension. The local release of pro-inflammatory neuropeptides and some cytokines may be the event that triggers and maintains the disease, causing hyperalgesia and allodynia. In the following phases, the impaired capillary permeability, the interstitial edema and the consequent hypoxia and local acidosis have been proposed as possible pathophysiological pathways. The local hyperactivity of the sympathetic nervous system supposed in the past has not be confirmed and the hypothesis of an altered nociceptive processing at CNS level has limited evidences in acute phases of the disease. The steady bone involvement could be confirmed by the efficacy of bisphosphonates in the treatment of early disease.

Intravenous neridronate in the treatment of acute painful knee osteoarthritis: a randomized controlled study.

OBJECTIVE: The aim of this randomized, double-blind, placebo-controlled study was to assess the efficacy of i.v. neridronate in controlling pain in patients with acute painful knee OA. METHODS: Sixty-four patients with acute knee pain (<3 months duration) suffering from knee OA with an MRI showing bone marrow lesions (BMLs) were randomized to receive either neridronate 100 mg given four times over 10 days or placebo. After 50 days the patients underwent clinical assessment and a further MRI was performed. Primary outcome was pain changes measured by a visual analogue scale (VAS; range 0-100). Secondary endpoints were WOMAC pain score, McGill pain questionnaire and 36-Item Short Form Health Survey. BMLs were evaluated by whole-organ MRI score. RESULTS: At the day of the last infusion the VAS decreased significantly more in the neridronate group [from 59.0 (s.d. 14.7) to 30.4 (s.d. 15.6); -48.4%; P < 0.001]. Fifty days later the VAS remained unchanged in the placebo group, while a further significant decrease was observed in the neridronate group [from 30.4 (s.d. 15.6) to 9.4 (s.d. 10.8); -69.1%; P < 0.001]. Significant improvements compared with the placebo group were found for most of the other indices of pain and quality of life. The BMLs score in the neridronate group showed significant decreases compared with basal values and those of the placebo-treated patients. Four months after the treatment, 72% of the placebo-treated patients resumed analgesic or anti-inflammatory drugs, but only 12.9% resumed treatment in the neridronate group. CONCLUSION: In patients with acute painful knee OA, four infusions of neridronate are associated with a clinically relevant pain benefit. TRIAL REGISTRATION: ClinicalTrials.gov (http://clinicaltrials.gov), NCT01803360.

Bisphosphonates in Complex Regional Pain syndrome type I: how do they work?

Complex Regional Pain syndrome type I (CRPS-I) is a disease characterised by extreme pain for which no gold-standard treatment exists to date. In recent years a possible role for bisphosphonates in the treatment of CRPS-I has been proposed. These drugs were first used for their effect in decreasing pain in bone diseases in which bisphosphonates act through their antiosteoclastic properties (metastatic disease, Paget disease, myeloma). In CRPS-I, enhanced osteoclastic activity has never clearly been demonstrated and the benefit shown is possibly exerted by different mechanisms of action. In this paper we review other conjectural mechanisms involved in reducing pain intensity and improving clinical signs and functional status in these patients. The results of most studies on this topic show that bisphosphonates may be effective in the early phases of the disease, when scintigraphic bone scan more frequently shows a local radiotracer accumulation that possibly means a high local concentration of the drug. These features probably represent the required conditions by which bisphosphonates might modulate various inflammatory mediators that are upregulated in CRPS-I. Patients in whom a scintiscan is often negative (long-standing disease or a primarily cold disease) could be less responsive to this treatment. With these limitations, bisphosphonates appear to present a therapeutic strategy that has been proven to reliably offer benefits in patients with CRPS-I.

Treatment thresholds for osteoporosis and reimbursability criteria: perspectives associated with fracture risk-assessment tools.

The definition of osteoporosis was based for several years on bone mineral density values, which were used by most guidelines for defining treatment thresholds. The availability of tools for the estimation of fracture risk, such as FRAX™ or its adapted Italian version, DeFRA, is providing a way to grade osteoporosis severity. By applying these new tools, the criteria identified in Italy for treatment reimbursability (e.g., "Nota 79") are confirmed as extremely conservative. The new fracture risk-assessment tools provide continuous risk values that can be used by health authorities (or "payers") for identifying treatment thresholds. FRAX estimates the risk for "major osteoporotic fractures," which are not counted in registered fracture trials. Here, we elaborate an algorithm to convert vertebral and nonvertebral fractures to the "major fractures" of FRAX, and this allows a cost-effectiveness assessment for each drug.

The association between osteoporosis and hypertension: the role of a low dairy intake.

Hypertension and related cardiovascular diseases are reported to be associated with osteoporosis. A nutritional pathway related to dairy intake has been postulated for both diseases. The aim of this study was to assess calcium intake from dairy sources as a possible pathogenic link between osteoporosis and hypertension. This was a cross-sectional observational study performed on 3,301 postmenopausal women referred for a densitometry screening. Osteoporosis was diagnosed by lumbar dual-energy X-ray absorptiometry and hypertension was defined by blood pressure data and/or the use of antihypertensive medication. Dairy food consumption was evaluated using a weekly food-frequency questionnaire. The odds of being affected by osteoporosis, hypertension, or both diseases were calculated for quartiles of dairy intake by logistic regression analyses. Women with hypertension were affected more frequently by osteoporosis (33.2 vs. 23.3 %; p = 0.000), and there was a higher prevalence of hypertension among women with osteoporosis (32.2 vs. 22.5 %; p = 0.000). The proportion of women with hypertension, osteoporosis, and both diseases significantly increased across decreasing quartiles of dairy intake. A dairy intake in the lowest quartile was a significant predictor of osteoporosis [OR (95 % CI): 1.43 (1.12, 1.82)] and hypertension [OR (95 % CI): 1.46 (1.15, 1.85)] when compared to the highest quartile. Similarly, a low dairy intake was associated with increased odds to have both the diseases [OR (95 % CI): 1.60 (1.10, 2.34)]. From these results we conclude that osteoporosis and hypertension are associated in postmenopausal women, and a low dairy intake may increase the risk of both diseases, acting as a possible pathogenic link.

Treatment of complex regional pain syndrome type I with neridronate: a randomized, double-blind, placebo-controlled study.

OBJECTIVE: Complex regional pain syndrome type I (CRPS-I) is a severely disabling pain syndrome for which no definite treatment has been established. The aim of this multi-centre, randomized, double-blind placebo-controlled trial was to test the efficacy of the amino-bisphosphonate neridronate in patients with CRP-I. METHODS: Eighty-two patients with CRP-I at either hand or foot were randomly assigned to i.v. infusion of 100 mg neridronate given four times over 10 days or placebo. After 50 days the former placebo patients were given open label the same regimen of neridronate. RESULTS: Within the first 20 days, visual analogue scale (VAS) score decreased significantly more in the neridronate group. In the following 20 days, VAS remained unchanged in the placebo group and further decreased in the active group by 46.5 mm (95% CI -52.5, -40.5) vs 22.6 mm (95% CI -28.8, -16.3) for placebo group (P < 0.0001). Significant improvements vs placebo were observed also for a number of other indices of pain and quality of life. During the open-extension phase in the formerly placebo group the results of treatment were superimposable on those seen during the blind phase in the active group. A year later none of the patients was referring symptoms linked to CRPS-I. CONCLUSION: In patients with acute CRPS-I, four i.v. infusions of neridronate 100 mg are associated with clinically relevant and persistent benefits. These results provide conclusive evidence that the use of bisphosphonates, at appropriate doses, is the treatment of choice for CRPS-I. TRIAL REGISTRATION: EU Clinical Trials Register, https://www.clinicaltrialsregister.eu/, 2007-003372-18.

Determinants and effects of vitamin D supplementation on serum 25-hydroxy-vitamin D levels in patients with rheumatoid arthritis.

OBJECTIVES: Osteoporosis (OP) and increased risk of fracture are relevant features in patients with rheumatoid arthritis (RA). Low levels of serum vitamin D are frequently reported and correlate with a higher RA activity. This study evaluated factors related with the prescription of vitamin D supplements in RA patients and variables influencing the achievement of adequate vitamin D levels. METHODS: Study population was made up by 1168 consecutive RA patients from 22 Italian rheumatology centers. Demographic and clinical variables data were collected and 25OH serum vitamin D was measured in all patients. Insufficient serum 25OH vitamin D levels were defined as values lower than 20 ng/mL. RESULTS: The majority of patients (56.0%) was not taking vitamin D supplements. Among the 514 supplemented patients, 196 (38.1%) were taking insufficient dosages (≤440 IU/day). Variables related with the prescription of supplements were older age, female sex, previous bone density assessment and OP diagnosis. Among the 318 patients using daily supplements ≥800 IU, 88 patients (27.7%) did not reach adequate levels of vitamin D. In these patients a higher HAQ score (OR for 1 point=1.62, 95% CI: 1.06-2.49; p=0.03) and poor sun exposure (OR=2.38, 95% CI: 1.05-5.55; p=0.04) were predictors of vitamin D insufficiency. CONCLUSIONS: Vitamin D deficiency is common in patients with RA, even in patients who are regularly using supplements. Vitamin D supplementation is often ineffective even at the recommended dose of 800 IU/day in more disabled patients.

Relationship of focal erosions, bone mineral density, and parathyroid hormone in rheumatoid arthritis.

OBJECTIVE: To investigate the relationship among focal bone erosions and bone mineral density (BMD), 25(OH) vitamin D (25OHD), and parathyroid hormone (PTH) values in patients with rheumatoid arthritis (RA). METHODS: The study included 1191 RA patients (1014 women, 177 men, mean age 58.9 ± 11.1 yrs) participating in a multicenter, cross-sectional study. RESULTS: Radiographic evidence of typical bony erosions on hands or forefeet was found in 64.1% of patients. In those with bone erosions as compared to those without, mean BMD Z score values were significantly lower at both the spine (-0.74 ± 1.19 vs -0.46 ± 1.31; p = 0.05) and the hip (-0.72 ± 1.07 vs -0.15 ± 1.23; p < 0.001). In the subgroup of patients not taking vitamin D supplements, PTH levels were significantly higher in those with erosive arthritis (25.9 ± 14.0 vs 23.1 ± 11.6 pg/ml; p = 0.01); whereas the 25OHD concentrations were very similar in the 2 groups. The mean differences for BMD and PTH among the erosive and nonerosive RA remained statistically significant when values were simultaneously adjusted for all disease and mineral metabolism factors (i.e., age, sex, menopause, disease duration, Disease Activity Score 28-joint count, Health Assessment Questionnaire, activities of daily living, Steinbrocker functional state, glucocorticoid therapy, body weight, and bisphosphonate treatment). CONCLUSION: Our results suggest that the presence of bone erosions in RA correlates with low BMD levels and high PTH levels, and that these associations are independent of the degree of functional impairment and other common determinants of bone mass and mineral metabolism in adults with RA. These findings suggest that treatments to prevent bone loss or suppress PTH levels might positively affect the progression of bone erosions in RA.