Sindrome da insensitività completa agli androgeni e massa ossea. Valutazione basale e longitudinale dopo oltre 12 mesi di terapia estrogenica

L’osso è un tessuto target per estrogeni ed androgeni ma l’azione singola e la sinergia tra i due non sono compresi interamente. Le donne affette da Sindrome da Insensititvità Completa agli Androgeni (CAIS) hanno un cariotipo 46XY ma presentano una completa inattività del recettore degli androgeni. Nello studio abbiamo valutato la densità minerale ossea (BMD) in un gruppo di donne adulte CAIS sottoposte a gonadectomia al momento della prima visita e dopo almeno 12 mesi di terapia estrogenica. Il principale obiettivo è stato di valutare se, nelle donne CAIS, una ottimale estrogenizzazione fosse sufficiente a mantenere/ripristinare una adeguata BMD. 24 donne CAIS sono state sottoposte a DXA lombare e femorale all'arruolamento nello studio (t1), dopo terapia estrogenica di 12mesi(t2) e oltre (t>2). Sono state valutate: BMD(g/cm2) e Zscore lombare e femorale (a t1,t2 e t>2) E’ stato considerato se fossero rilevanti l’essere (gruppo1) o meno (gruppo 2) in terapia ormonale al t1 e l’età della gonadectomia. Risultati: Al t1 BMD e Zscore lombari e femorale erano significativamente ridotti rispetto alla popolazione controllo nel campione totale (lombare 0,900+0,12; -1,976+0,07, femorale 0,831 + 0,14; -1,385+0,98), nel gruppo 1 (lombare 0,918+0,116;-1,924+0,79, femorale 0,824+0,13;-1,40+1,00) e nel gruppo 2 (lombare 0.845+0,11 -2,13+1,15, femorale 0,857+0,17;-1,348+1,05) Al t2 e t>2 la BMD lombare è risultata significativamente aumentata (p=0,05 e p=0,02). Zscore lombare, BMD e Zscore femorale non hanno dimostrato variazioni significative. L’aver effettuato la gonadectomia in età post puberale è associato a Zscore lombare e femorale più elevati al t1. Nelle donne CAIS la terapia estrogenica è indispensabile per prevenire un'ulteriore perdita di BMD ma, da sola, non sembra in grado di ripristinare normali valori di BMD.I risultati del nostro studio supportano la tesi che gli androgeni, mediante l’azione recettoriale, abbiano un' azione diretta nel raggiungere e mantenere la BMD.

Periodontitis: a future risk of acute coronary syndrome? A follow-up study over 3 years

BACKGROUND: Periodontitis has been associated with cardiovascular disease. We assess if the recurrence of acute coronary syndrome (ACS) could be predicted by preceding medical and periodontal conditions. METHODS: A total of 165 consecutive subjects with ACS and 159 medically healthy, matched control subjects were examined and followed for 3 years. Periodontitis was defined by alveolar bone loss. Subgingival microbial samples were studied by the checkerboard DNA-DNA hybridization method. RESULTS: The recurrence of ACS was found in 66 of 165 (40.0%) subjects, and a first ACS event was found in seven of 159 (4.4%) subjects among baseline control subjects. Subjects who later had a second ACS event were older (P <0.001). Significantly higher serum levels of high-density lipoprotein (P <0.05), creatinine (P <0.01), and white blood cell (WBC) counts (P <0.001) were found in subjects with future ACS. Periodontitis was associated with a first event of ACS (crude odds ratio [OR]: 10.3:1; 95% confidence interval [CI]: 6.1 to 17.4; P <0.001) and the recurrence of ACS (crude OR: 3.6:1; 95% CI: 2.0 to 6.6; P <0.001). General linear modeling multivariate analysis, controlling for age and the prediction of a future ACS event, identified that WBC counts (F = 20.6; P <0.001), periodontitis (F = 17.6; P <0.001), and serum creatinine counts (F = 4.5; P <0.05) were explanatory of a future ACS event. CONCLUSIONS: The results of this study indicate that recurrent ACS events are predicted by serum WBC counts, serum creatinine levels, and a diagnosis of periodontitis. Significantly higher counts of putative pathogens are found in subjects with ACS, but these counts do not predict future ACS events.

Prediction of hip and hand fractures in older persons with or without a diagnosis of periodontitis

Purpose: In a prospective study, we assessed if a diagnosis of osteoporosis and periodontitis could predict hip and hand fractures in older persons. Materials and methods: Bone density was assessed by a Densitometer. Periodontitis was defined by evidence of alveolar bone loss. Results: 788 Caucasians (52.4% women, overall mean age: 76 years, S.D. +/- 9.0, range: 62 to 96) were enrolled and 7.4% had a hip/hand fracture in 3 years. Calcaneus PIXI T-values < - 1.6 identified osteoporosis in 28.2% of the older persons predicting a hip/hand fracture with an odds ratio of 3.3:1 (95% CI: 1.9, 5.7, p < 0.001). Older persons with osteoporosis had more severe periodontitis (p < 0.01). Periodontitis defined by >= 30% of sites with >= 5 mm distance between the cemento-enamel junction (CEJ) and bone level (ABL) was found in 18.7% of the older persons predicting a hip/hand fracture with an odds ratio of 1.8:1 (95% CI: 1.0, 3.3, p < 0.05). Adjusted for age, the odds ratio of a hip/hand fracture in older persons with osteoporosis (PIXI T-value <-2.5) and periodontitis was 12.2:1 (95% CI: 3.5, 42.3, p < 0.001). Conclusions: Older persons with osteoporosis and periodontitis have an increased risk for hip/hand fractures

The effect of different implant neck configurations on soft and hard tissue healing: a randomized-controlled clinical trial

Objective: To compare the soft and hard tissue healing and remodeling around tissue-level implants with different neck configurations after at least 1 year of functional loading. Material and methods: Eighteen patients with multiple missing teeth in the posterior area received two implants inserted in the same sextant. One test (T) implant with a 1.8 mm turned neck and one control (C) implant with a 2.8 mm turned neck were randomly assigned. All implants were placed transmucosally to the same sink depth of approximately 1.8 mm. Peri-apical radiographs were obtained using the paralleling technique and digitized. Two investigators blinded to the implant type-evaluated soft and hard tissue conditions at baseline, 6 months and 1 year after loading. Results: The mean crestal bone levels and soft tissue parameters were not significantly different between T and C implants at all time points. However, T implants displayed significantly less crestal bone loss than C implants after 1 year. Moreover, a frequency analysis revealed a higher percentage (50%) of T implants with crestal bone levels 1–2 mm below the implant shoulder compared with C implants (5.6%) 1 year after loading. Conclusion: Implants with a reduced height turned neck of 1.8 mm may, indeed, lower the crestal bone resorption and hence, may maintain higher crestal bone levels than do implants with a 2.8 mm turned neck, when sunk to the same depth. Moreover, several factors other than the vertical positioning of the moderately rough SLA surface may influence crestal bone levels after 1 year of function.

Osteoporosis and periodontitis in older subjects participating in the Swedish National Survey on Aging and Care (SNAC-Blekinge)

Abstract Objective. We assessed the relationships between (I) ultrasonography calcaneus T-scores (PIXI) and mandibular cortex characteristics on oral panoramic radiographs in older subjects; and (II) osteoporosis and periodontitis. Material and methods. We examined 778 subjects (53% women) aged 59-96 years. Periodontitis was defined by alveolar bone loss assessed from panoramic radiographs. Results. PIXI calcaneus T-values ?-2.5 (osteoporosis) were found in 16.3% of women and in 8.1% of men. PIXI calcaneus T-values <-1.6 (osteoporosis, adjusted) were found in 34.2% of women and in 21.4% of men. The age of the subjects and PIXI T-values were significantly correlated in women (Pearson's r = 0.37, P < 0.001) and men (Pearson's r = 0.19, P < 0.001). Periodontitis was found in 18.7% of subjects defined by alveolar bone level ?5 mm. Subjects with osteoporosis defined by adjusted PIXI T-values had fewer remaining teeth [mean difference 4.1, 95% confidence interval (CI) -1.1 to -6.5, P < 0.001]. The crude odds ratio (OR) of an association between the panoramic assessment of mandibular cortex erosions as a sign of osteoporosis and the adjusted T-value (T-value cut-off <-1.6) was 4.8 (95% CI 3.1-7.2, P < 0.001; Pearson ?(2) = 60.1, P < 0.001). A significant OR between osteoporosis and periodontitis was only found in women for the T-value cut-off ?-2.5 (crude OR 1.8, 95% CI 1.1-3.3, P < 0.03). Conclusions. An association between osteoporosis and periodontitis was only confirmed in women. The likelihood that the mandibular cortex index agrees with adjusted PIXI T-values is significant.

Unconventional implants for distal cantilever fixed full-arch prostheses: a long-term evaluation of four cases

Excessive cantilever lengths of fixed implant-supported prostheses may have functional and biomechanical disadvantages. This study reports the clinical outcomes of unconventional implants placed for distal support of a fixed implant-supported prostheses. Seven extraoral implants with intraosseous lengths of 2.5 to 4.0 mm were placed in four patients. Distal cantilevers had a mean length of 29.8 mm (range, 18.6 to 39.3 mm). No bone loss or other adverse events were found. The prosthetic plan was maintained in all patients. Within the limits of the employed research design, this concept seems to be a successful option for fixed complete implant-supported prosthesis treatment.

Differential effects of dexamethasone on the chondrogenesis of mesenchymal stromal cells: influence of microenvironment, tissue origin and growth factor

Mesenchymal stromal cells (MSCs), which reside within various tissues, are utilized in the engineering of cartilage tissue. Dexamethasone (DEX)--a synthetic glucocorticoid--is almost invariably applied to potentiate the growth-factor-induced chondrogenesis of MSCs in vitro, albeit that this effect has been experimentally demonstrated only for transforming-growth-factor-beta (TGF-β)-stimulated bone-marrow-derived MSCs. Clinically, systemic glucocorticoid therapy is associated with untoward side effects (e.g., bone loss and increased susceptibility to infection). Hence, the use of these agents should be avoided or limited. We hypothesize that the influence of DEX on the chondrogenesis of MSCs depends upon their tissue origin and microenvironment [absence or presence of an extracellular matrix (ECM)], as well as upon the nature of the growth factor. We investigated its effects upon the TGF-β1- and bone-morphogenetic-protein 2 (BMP-2)-induced chondrogenesis of MSCs as a function of tissue source (bone marrow vs. synovium) and microenvironment [cell aggregates (no ECM) vs. explants (presence of a natural ECM)]. In aggregates of bone-marrow-derived MSCs, DEX enhanced TGF-β1-induced chondrogenesis by an up-regulation of cartilaginous genes, but had little influence on the BMP-2-induced response. In aggregates of synovial MSCs, DEX exerted no remarkable effect on either TGF-β1- or BMP-2-induced chondrogenesis. In synovial explants, DEX inhibited BMP-2-induced chondrogenesis almost completely, but had little impact on the TGF-β1-induced response. Our data reveal that steroids are not indispensable for the chondrogenesis of MSCs in vitro. Their influence is context dependent (tissue source of the MSCs, their microenvironment and the nature of the growth-factor). This finding has important implications for MSC based approaches to cartilage repair.

Tumor necrosis factor-alpha: alternative role as an inhibitor of osteoclast formation in vitro

TNFalpha is known to stimulate the development and activity of osteoclasts and of bone resorption. The cytokine was found to mediate bone loss in conjunction with inflammatory diseases such as rheumatoid arthritis or chronic aseptic inflammation induced by wear particles from implants and was suggested to be a prerequisite for the loss of bone mass under estrogen deficiency. In the present study, the regulation of osteoclastogenesis by TNFalpha was investigated in co-cultures of osteoblasts and bone marrow or spleen cells and in cultures of bone marrow and spleen cells grown with CSF-1 and RANKL. Low concentrations of TNFalpha (1 ng/ml) caused a >90% decrease in the number of osteoclasts in co-cultures, but did not affect the development of osteoclasts from bone marrow cells. In cultures with p55TNFR(-/-) osteoblasts and wt BMC, the inhibitory effect was abrogated and TNFalpha induced an increase in the number of osteoclasts in a dose-dependent manner. Osteoblasts were found to release the inhibitory factor(s) into the culture supernatant after simultaneous treatment with 1,25(OH)(2)D(3) and TNFalpha, this activity, but not its release, being resistant to treatment with anti-TNFalpha antibodies. Dexamethasone blocked the secretion of the TNFalpha-dependent inhibitor by osteoblasts, while stimulating the development of osteoclasts. The data suggest that the effects of TNFalpha on the differentiation of osteoclast lineage cells and on bone metabolism may be more complex than hitherto assumed and that these effects may play a role in vivo during therapies for inflammatory diseases.

Glucocorticosteroid-induced spinal osteoporosis: scientific update on pathophysiology and treatment

Glucocorticosteroid-induced spinal osteoporosis (GIOP) is the most frequent of all secondary types of osteoporosis. The understanding of the pathophysiology of glucocorticoid (GC) induced bone loss is of crucial importance for appropriate treatment and prevention of debilitating fractures that occur predominantly in the spine. GIOP results from depressed bone formation due to lower activity and higher death rate of osteoblasts on the one hand, and from increase bone resorption due to prolonged lifespan of osteoclasts on the other. In addition, calcium/phosphate metabolism may be disturbed through GC effects on gut, kidney, parathyroid glands and gonads. Therefore, therapeutic agents aim at restoring balanced bone cell activity by directly decreasing apoptosis rate of osteoblasts (e.g., cyclical parathyroid hormone) or by increasing apoptosis rate of osteoclasts (e.g., bisphosphonates). Other therapeutical efforts aim at maintaining/restoring calcium/phosphate homeostasis: improving intestinal calcium absorption (using calcium supplementation, vitamin D and derivates) and avoiding increased urinary calcium loss (using thiazides) prevent or counteract a secondary hyperparthyroidism. Bisphosphonates, particularly the aminobisphosphonates risedronate and alendronate, have been shown to protect patients on GCs from (further) bone loss to reduce vertebral fracture risk. Calcitonin may be of interest in situation where bisphosphonates are contraindicated or not applicable and in cases where acute pain due to vertebral fracture has to be manage. The intermittent administration of 1-34-parathormone may be an appealing treatment alternative, based on its documented anabolic effects on bone resulting from the reduction of osteoblastic apoptosis. Calcium and vitamin D should be a systematic adjunctive measure to any drug treatment for GIOP. Based on currently available evidence, fluoride, androgens, estrogens (opposed or unopposed) cannot be recommended for the prevention and treatment of GIOP. However, substitution of gonadal hormones may be indicated if GC-induced hypogonadism is present and leads to clinical symptoms. Data using the SERM raloxifene to treat or prevent GIOP are lacking, as are data using the promising bone anabolic agent strontium ranelate. Kyphoplasty performed in appropriately selected osteoporotic patients with painful vertebral fractures is a promising addition to current medical treatment.

Peri-implant inflammation defined by the implant-abutment interface

An implant-abutment interface at the alveolar bone crest is associated with sustained peri-implant inflammation; however, whether magnitude of inflammation is proportionally dependent upon interface position remains unknown. This study compared the distribution and density of inflammatory cells surrounding implants with a supracrestal, crestal, or subcrestal implant-abutment interface. All implants developed a similar pattern of peri-implant inflammation: neutrophilic polymorphonuclear leukocytes (neutrophils) maximally accumulated at or immediately coronal to the interface. However, peri-implant neutrophil accrual increased progressively as the implant-abutment interface depth increased, i.e., subcrestal interfaces promoted a significantly greater maximum density of neutrophils than did supracrestal interfaces (10,512 +/- 691 vs. 2398 +/- 1077 neutrophils/mm(2)). Moreover, inflammatory cell accumulation below the original bone crest was significantly correlated with bone loss. Thus, the implant-abutment interface dictates the intensity and location of peri-implant inflammatory cell accumulation, a potential contributing component in the extent of implant-associated alveolar bone loss.

Adjunctive local antibiotic therapy in the treatment of peri-implantitis II: clinical and radiographic outcomes

AIM: To monitor over 12 months clinical and radiographic changes occurring after adjunctive local delivery of minocycline microspheres for the treatment of peri-implantitis. MATERIAL AND METHODS: In 25 partially edentulous subjects, 31 implants diagnosed with peri-implantitis were treated. Three weeks after oral hygiene instruction, mechanical debridement and local antiseptic cleansing using 0.2% chlorhexidine gel, baseline (Day 0) parameters were recorded. Minocycline microspheres (Arestin) were locally delivered to each implant site with bone loss and a probing pocket depth (PPD) >or=5 mm. Rescue therapy with Arestin was allowed at Days 180 and 270 at any site exhibiting an increase in PPD>or=2 mm from the previous visit. The following clinical parameters were recorded at four sites/implant at Day 0, 10, 30, 60, 90, 180, 270 and 360: PPD, clinical attachment level (CAL), bleeding on probing (BOP) and plaque index (PlI). RESULTS: Six implants in six subjects were either rescued or exited because of persisting active peri-implantitis. Successful implants showed a statistically significant reduction in both PPD and percentage of sites with BOP between baseline and Day 360 (P<0.05). At mesial implant sites, the mean PPD reduction amounted to 1.6 mm (95% CI: 0.9-2.2 mm, P<0.001) and was accompanied by a statistically significant reduction of the BOP value (P<0.001). Binary regression analysis showed that the clinical parameters and smoking history could not discriminate between successfully treated and rescued or exited implants at any observation time point. CONCLUSION: Non-surgical mechanical treatment of peri-implantitis lesions with adjunctive local delivery of microencapsulated minocycline led to positive effects on clinical parameters up to 12 months.

The Subgingival Microbiota in older subjects. Impact of Chlorhexidine Rinsing

Background: Periodontitis and caries are common diseases in older adults. Aims: To test if rinsing with chlorhexidine over five years has an impact on the subgingival microbiota. Methods: In a double blind randomized five years chlorhexidine rinse study clinical oral data and subgingival plaque samples were analyzed by the checkerboard DNA-DNA hybridization method. Results: At year 5 subject mean age was 71.2 years (S.D. + 4.1) (56.2% women). Only in subjects with no bone loss did the chlorhexidine rinse group subjects presented with lower total bacterial (DNA) counts (mean diff: 63.1 (x105), S.E diff + 30.1 (x105), 95%CI: 0.8 to 120.5 (x105), p<0.05) [(i.e.Lactobacillus acidophilicus (p<0.05) , Streptococcus oralis (p<0.05), Eikenella. corrodens (p< 0.05), C. gracilis (p<0.01), F.nucl.sp. nucleatum (p< 0.02), Fusobacterium nucl. sp. polymorphum (p<0.02), Neisseria mucosa (p<0.02), Leptothrichia buccalis (p<0.02), and Selenomonas noxia (p<0.050)]. Higher bacterial loads were found for the green (p<0.05), yellow (streptococci spp) (p<0.01), and the ‘other' complexes (p<0.01). Conclusions: Independent of probing pocket depth, older subjects carry a large variety of bacteria associated with periodontitis. The oral microbiota in older subjects is linked to alveolar bone loss and not to probing depth. Chlorhexidine may provide a benefit in preventing periodontitis in older persons.

Influence of various surface treatments on reosseointegration around contaminated implants

The similarity of periodontitis and peri-implantitis demands for the utilization of similar principles for the treatment. Different decontamination methods were available cleaning of implant surfaces contaminated with bacteria. The aim of the present study was to evaluate the effects of various decontamination methods on reosseointegration on contaminated implants. Six mongrel dogs were used. The mandibular 1st molars and all premolars were removed bilaterally. Three months later, experi- mental implants with different surface characters were installed in each sides of the mandible. The implant consisted of two parts; the implant body and an exchangeable intraosseous implant cylinder. After osseointegration, experimental peri-implantitis was induced by cotton ligatures until the bone loss reached the junction of the two segments of the implant. After debridement of the bone defects, three treatment models were performed; (i) contaminated cylinders were removed, pristine cylinders were placed; (ii) contaminated cylinders were cleaned in situ with saline and (iii) contaminated cylinders was removed, cleaned with saline, sterilized by autoclaving. All implants were covered with membranes. After 3 months, histological evaluations were accomplished. The results indicated that in situ saline therapy demonstrated a significant difference at SLA surfaces in bone-implant-contact. Treatment of contaminated implants in situ with saline resulted in resolution of peri-implantitis and bone fill in defects.

A systematic review of the 5-year survival and complication rates of implant-supported single crowns

OBJECTIVES: The objective of this systematic review was to assess the 5-year survival of implant-supported single crowns (SCs) and to describe the incidence of biological and technical complications. METHODS: An electronic MEDLINE search complemented by manual searching was conducted to identify prospective and retrospective cohort studies on SCs with a mean follow-up time of at least 5 years. Failure and complication rates were analyzed using random-effects Poisson's regression models to obtain summary estimates of 5-year proportions. RESULTS: Twenty-six studies from an initial yield of 3601 titles were finally selected and data were extracted. In a meta-analysis of these studies, survival of implants supporting SCs was 96.8% [95% confidence interval (CI): 95.9-97.6%] after 5 years. The survival rate of SCs supported by implants was 94.5% (95% CI: 92.5-95.9%) after 5 years of function. The survival rate of metal-ceramic crowns, 95.4% (95% CI: 93.6-96.7%), was significantly (P=0.005) higher than the survival rate, 91.2% (95% CI: 86.8-94.2%), of all-ceramic crowns. Peri-implantitis and soft tissue complications occurred adjacent to 9.7% of the SCs and 6.3% of the implants had bone loss exceeding 2 mm over the 5-year observation period. The cumulative incidence of implant fractures after 5 years was 0.14%. After 5 years, the cumulative incidence of screw or abutment loosening was 12.7% and 0.35% for screw or abutment fracture. For supra-structure-related complications, the cumulative incidence of ceramic or veneer fractures was 4.5%. CONCLUSION: It can be concluded that after an observation period of 5 years, high survival rates for implants and implant-supported SCs can be expected. However, biological and particularly technical complications are frequent.

Immunization of Macaca fascicularis against experimental periodontitis using a vaccine containing cysteine proteases purified from Porphyromonas gingivalis

INTRODUCTION: Periodontitis is a common infectious disease to which Porphyromonas gingivalis has been closely linked, in which the attachment tissues of the teeth and their alveolar bone housing are destroyed. We conducted a study to determine if immunization using a purified antigen could alter the onset and progression of the disease. METHODS: Using the ligature-induced model of periodontitis in Macaca fascicularis, we immunized five animals with cysteine protease purified from P. gingivalis and used an additional five animals as controls. Alveolar bone loss was measured by digital subtraction radiography. RESULTS: Immunization induced high titers of specific immunoglobuin G serum antibodies that were opsonic. Total bacterial load, levels of P. gingivalis in subgingival plaque and levels of prostaglandin E(2) in gingival crevicular fluid were significantly reduced. Onset and progression of alveolar bone loss was inhibited by approximately 50%. No manifestations of toxicity were observed. CONCLUSIONS: Immunization using a purified protein antigen from P. gingivalis inhibits alveolar bone destruction in a ligature-induced periodontitis model in M. fascicularis.