Surgical therapy for medication-related osteonecrosis of the jaw in osteoporotic patients treated with antiresorptive agents.

BACKGROUND: Medication - related osteonecrosis of the jaw (MRONJ) is a rare but serious complication of antiresorptive and/or antiangiogenic therapy. It mainly affects oncological patients, however, it can occur in patients with metabolic bone diseases, although this is less frequent. These lesions not only significantly impair the quality of life but can also have impact on the treatment of any underlying disease. In some rare cases MRONJ can be life-threatening. There is still no ideal consensus for treatment, though surgical therapy has been mostly preferred in recent years. MATERIALS AND METHODS: A monocentric retrospective evaluation of surgical therapy of MRONJ in osteoporotic patients, treated in the time period 3/2014-3/2018 using the uniform department-specific protocol. RESULTS: 26 osteoporotic patients with 32 MRONJ lesions of stage 1 (9%), stage 2 (75%) and stage 3 (16%) were treated surgically. The maxilla: mandibula ratio was 1:2.2, in 19% of patients there was multiple jaw involvement. 69.2% of patients had received bisphosphonates, 15.4% denosumab and 15.4% had a history of both types of antiresorptive treatment. Complete healing was observed in all patients, in 9% of cases by secondary intention in the mean period of 6 weeks. The mean follow-up was 20.5 months. CONCLUSION: The presented protocol for surgical therapy was effective in the management of all MRONJ stages in the osteoporotic patients described here. The surgery is indicated as an early treatment to prevent complications and the progression of the lesions. It leads to improvement in quality of life and option to resume antiresorptive therapy if interrupted.

Incidentally diagnosed melorheostosis of upper limb: case report.

BACKGROUND: Melorheostosis is quite a rare bone disease with still unclear ethiology. Although multifocal affection is highly debilitating with unfavorable prognosis, there is no clear consensus about therapeutical approach. There is still insufficient evidence in the literature for almost a century after the first description. Affected bone has a typical appearance of melting wax. Diagnosis is usually incidental with pain as a leading symptom. Diagnosis itself is relatively easy, routine X-ray examination is sufficient. Even though it could be easily overlooked and mistaken with other diseases. Melorheostosis is incurable, the therapy is mostly focused on maintaining patient quality of life. Presented case is unique in terms of extent of the affection (index finger, metacarp shaft, carpal bones, forearm, humerus and whole scapula) in combination with osteopoikilotic islands in other 3 regions (vertebrae, manubrium sterni and left collar bone). Currently there is only one such a case published in the literature (Campbell), but without osteopoikilotic islands. CASE PRESENTATION: Melorheostosis was diagnosed in 26-year old female after injury as an incidental finding. This was quite surprising as the patient already suffered by limited movement in the upper limb and pain before the injury. Detailed examination were performed to confirm the diagnosis, no family history was found. Pharmacotherapy with bisphosphonates, non-steroidal antirheumatics and vasodilatans/rheologic drugs seemed to be effective to maintain the relatively good quality of patient life and good performance in daily routine. Questionable is further development of patient performance status and sustainability of conservative treatment in the long term follow up. CONCLUSION: Conservative treatment with bisphopshonates and COX-2 inhibitors in combination with naftidrofuryl can delay surgery solution.

[Calcium, vitamin D and health]. / Kalcium, vitamin D a zdraví

The authors describe briefly recent views on physiological, pathological and practical aspects of calcium and vitamin D. The sources of calcium are the nutrients, mammal milk and milk products as well as pharmaceutical products. Their beneficial and potentially hazardous effects are discussed. The insufficiency of vitamin D [25(OH)D3] is a global health problem and the necessity of monitoring of this hepatic metabolite (as a marker) is emphasized due to its role in physio-logical and pathological processes.Key words: calcium - physiological and pathophysiological effects - vitamin D.

Single-dose and steady state pharmacokinetics of CSA and two main primary metabolites, AM1 and AM4n in patients with rheumatic/autoimmune diseases.

BACKGROUND: Cyclosporine A (CsA) is an immunomodulatory agent used in standard immunosuppressive regimens in solid organ transplantations as well as in the treatment of autoimmune diseases such as rheumatoid arthritis (RA), systemic lupus and psoriasis. Its immunosuppressive activity is primarily due to parent drug. However, following oral administration, absorption is incomplete and varies between individuals. Further, there is a dearth of pharmacokinetic data for CsA in autoimmune patients compared to transplant recipients. AIM: The goal of this study was to investigate the single-dose and steady state pharmacokinetics of CsA and two main primary metabolites, AM1 and AM4N, in patients with rheumatic/autoimmune diseases. METHODS: Thirty-eight subjects, average age (years± SD) 46.8 (±11.6) years with rheumatoid arthritis, systemic lupus erythematosus, psoriatic arthritis, ankylosing spondylitis and undifferentiated SpA were included in an observational open study. The single dose pharmacokinetics (area under the concentration-time curve of CsA and its metabolites (AUC) and other PK parameters) were determined over a 24 h period following oral administration of 1.3 mg/kg oral CsA. Two CsA formulations-Neoral and the Czech generic substitute Consupren®, were used. Pharmacokinetic analysis was performed on all 38 patients after administration of a single dose of CsA (1.34 mg/ kg/day). In 12 patients only, a second series of blood samples was taken to calculate monitored PK parameters under steady state conditions. RESULTS: Pharmacokinetic assessment showed AUC(0-24) 3009.66 ± 1449.78 ng/ml.h and C(max) 827.84 ± 425.84 after administration of a single dose of CSA, AUC(0-24) 3698.50 ± 2147 ng/ml.h and C(max) 741 ± 493 ng/ml after repeated dose. The proportion of the AM1 metabolite (AUC(0-24)) after a single dose of CsA corresponded to 40% of the parent compound and to approximately 35% of the parent compound in steady state conditions. The proportion of AM4N metabolite was low in both conditions and represented only 3 and 4.5% after a single dose and at steady state, respectively. CONCLUSION: The pharmacokinetic data (AUC(CsA), C(max)) for the whole 24 h interval were similar to the published findings, mainly under steady state conditions. The AM1 (AUC(0-24)) after a single dose of CsA and in steady state conditions represented about 40% of the parent drug. The ratio of AM4N metabolite was low in both conditions.

Bisphosphonates in calcific aortic stenosis: association with slower progression in mild disease--a pilot retrospective study.

OBJECTIVES: An association between aortic valve calcification and osteoporosis has been observed. The aim of this study was to assess the association between bisphosphonate treatment for osteoporosis and the progression of calcific aortic stenosis (AS). METHODS: A retrospective study of patients with AS (mean gradient ≥10 mm Hg), preserved renal function and two echocardiographies >8 months apart was performed. The patients were divided into those treated with bisphosphonates for osteoporosis and those not treated and then subdivided into mild (mean gradient <30 mm Hg) and moderate-to-severe AS groups. We compared the annualized gradient change between the groups and identified predictors of AS progression. RESULTS: We analyzed the outcomes of 103 patients (51% females, age 68 ± 10 years, follow-up 29 ± 13 months), of whom 57 had mild and 46 moderate-to-severe AS. Bisphosphonates were taken by 28 patients, of whom 22 had mild and 6 moderate-to-severe AS. In the patients with mild AS, the annualized mean gradient change was lower in the bisphosphonate-treated than in the untreated patients (0.1 ± 3.3 vs. 2.8 ± 3.3 mm Hg/year; p = 0.002) and was negatively associated with bisphosphonate treatment (ß coefficient -2.36%, 95% confidence interval -4.47 to -0.26; p = 0.028) independent of age, gender and baseline gradient. CONCLUSION: Bisphosphonate treatment was independently associated with slower progression of mild AS in patients with preserved renal function.

Effect of alendronate therapy in children with osteogenesis imperfecta.

OBJECTIVE: To evaluate the effect of orally administered alendronate in children with osteogenesis imperfecta. METHODS: Thirty children (16 girls and 14 boys; mean age at baseline 10.7 +/- 6.0 years; range 4-16 years) with osteogenesis imperfecta type I (n = 22), III (n = 2), or IV (n = 6) were treated with alendronate (5 mg/day in patients aged 4-10 years and 10 mg/day in children >10 years of age) for 3 years. RESULTS: After 1 year of alendronate therapy we observed a significant increase in areal and volumetric bone mineral density Z-scores (from -2.03 +/- 1.51 to -1.04 +/- 1.20, and from -1.91 +/- 1.38 to -1.33 +/- 1.30, respectively, P < 0.001), together with a significant drop in fracture rate (from 3.77 +/- 1.57 to 0.13 +/- 0.57, P < 0.000001), relief of chronic pain (from 3.83 +/- 1.44 days of pain/week to 0.73 +/- 0.77, P < 0.000001) and improvement in ambulation/mobility (P < 0.00002). After additional 2 years of therapy there were no further significant changes in these parameters, however the improvement was still remarkable in comparison to the pretreatment values (P < 0.003, P < 0.004, P < 0.000001, P < 0.000001 and P < 0.00001, respectively). A significant drop in markers of bone turnover (urinary deoxypyridinoline and serum osteocalcin) occurred after 3 years of therapy (P < 0.003 and 0.004, respectively). No adverse reactions were observed throughout the treatment. CONCLUSIONS: Alendronate has positively influenced quality of life in paediatric patients with osteogenesis imperfecta. Bisphosphonate therapy should be used only in the context of a well-defined protocol.