Impacto do uso sistêmico de estatinas e de bisfosfonatos nos tecidos periodontais: revisão narrativa / Impact of the systemic use of statins and bisphosphonates in the periodontal tissues: narrative review

Introdução: A literatura tem apontado uma possível relação entre diversas condições sistêmicas e as doenças periodontais. Dentro das doenças sistêmicas que podem gerar o uso crônico de medicamentos, com potencial associação com as doenças periodontais, destacam-se a hipercolesterolemia e o uso de estatinas; e as doenças do metabolismo ósseo e o uso de bisfosfonatos. Objetivo: Dessa maneira, o presente estudo objetivou revisar a literatura sobre o efeito das estatinas e dos bisfosfonatos nos parâmetros clínicos e radiográficos periodontais de indivíduos adultos. Resultados: Apenas estudos observacionais em humanos foram incluídos. Um estudo mostrou que, em pacientes que apresentam doença periodontal e usam estatina, houve 37% menos bolsas periodontais (profundidade de sondagem ≥4mm) quando comparadas aos que não utilizam a medicação, além de apresentarem menor índice de carga inflamatória e menor perda de inserção clínica. Em relação aos bisfosfonatos em indivíduos com doenças que envolvem o metabolismo ósseo, sugere-se que a utilização do fármaco tem obtido resultados positivos nos parâmetros periodontais, como menores sinais clínicos de inflamação gengival, menor profundidade de sondagem, menor perda de inserção clínica e maior nível de osso alveolar, quando comparados aos que nunca realizam essa terapia. Conclusão: Dessa forma, as estatinas e os bisfosfonatos apresentam efeitos promissores, em pacientes sob tratamento para suas respectivas condições sistêmicas, na melhoria dos parâmetros periodontais, porém é importante salientar que são necessários mais estudos sobre o assunto para melhor entender os reais efeitos a longo prazo do uso desses fármacos.(AU)

Introduction: The literature showed a possible relationship between several systemic conditions and periodontal diseases. Within the systemic diseases that can generate the chronic use of these drugs, potentially related with periodontal diseases, it may be cited the hypercholesterolemia and the use of statins; and bone metabolism diseases and the use of bisphosphonates. Objective: In this sense, the present study aimed to review the literature about the effect of statins and bisphosphonates in the periodontal parameters of adults individuals. Results: Only observational studies in humans were included. A study showed that, in patients with periodontal disease and users of statins, there 37% fewer periodontal pockets (probing depth ≥4mm) when compared to those who do not use the medication, as well as having a lower rate of inflammatory burden and less loss of clinical insertion. Regarding the bisphosphonates in individuals diagnosed with diseases involving bone metabolism, it was suggested that the use of the drug has obtained positive results in periodontal parameters, such as a greater absence of plaque, less clinical signs of gingival inflammation, less probing depth, lower level of clinical insertion and higher level of alveolar bone when compared to those who never undergo this therapy. Conclusion: Thus, statins and bisphosphonates have promising effects in patients under treatment for their respective systemic condition in improving periodontal parameters, but it is important to emphasize that further studies on the subject are needed to better understand the long-term effects of the use of these drugs.(AU)

VIH y salud ósea / HIV and bone health

Con el advenimiento de la terapia antirretroviral, el pronóstico y la sobrevida de los pacientes infectados con el virus de la inmunodeficiencia humana (VIH) han cambiado de manera radical, por lo cual en la actualidad se evidencia un aumento en el riesgo de padecer enfermedades no relacionadas con el VIH como, por ejemplo, la osteoporosis. La disminución de la densidad mineral ósea (DMO) se observa en el 40-90% de las personas infectadas por el VIH, con una prevalencia de osteopenia y osteoporosis del 52 y 15%, respectivamente. Esta población de pacientes tiene un mayor riesgo de fracturas (60%) en comparación con personas no infectadas y un riesgo de fracturas vertebrales 2,3 veces mayor que en la población general. El tenofovir fumarato se asoció con un aumento de pérdida renal de fósforo e hiperparatiroidismo secundario. El efavirenz y los inhibidores de proteasas (IP) afectan el metabolismo de la vitamina D; actúan a nivel enzimático aumentando la expresión de la enzima CYP24 que lleva a producción de vitamina D inactiva. El FRAX es una herramienta sencilla y accesible, por lo que su uso está recomendado en pacientes con VIH. Además de las medidas higiénico-dietéticas, actividad física, calcio y vitamina D, el uso de bifosfonatos está indicado en el tratamiento de la osteoporosis en estos pacientes. (AU)

With the advent of antiretroviral therapy, the prognosis and survival of patients infected with the human immunodeficiency virus (HIV) have radically changed, which is why there is now evidence of an increased risk of suffering from diseases not related to HIV such as osteoporosis. The decrease in bone mineral density (BMD) is observed in 40-90% of people infected with HIV, with a prevalence of osteopenia and osteoporosis of 52 and 15%, respectively. This patient population has a 60% higher risk of fractures compared to uninfected people and a risk of vertebral fractures 2.3 times higher than in the general population. Tenofovir fumarate administration is associated with increased renal phosphorus loss and secondary hyperparathyroidism. Efavirenz and protease inhibitors (IP) affect the metabolism of vitamin D, they act at the enzymatic level by increasing the expression of the CYP24 enzyme that leads to the production of inactive vitamin D. The FRAX is a simple and accessible tool, so its use is recommended in patients with HIV and in addition to dietary hygiene measures, physical activity, calcium, and vitamin D, the use of bisphosphonates is indicated in the treatment of osteoporosis in these patients. (AU)

Effect of alendronate on healing of bone defect and gingival tissue in osteopenic rats / Efecto del alendronato en la reparación de defectos óseos y tejido gingival en ratas con osteopenia

The aim was to evaluate bone repair and gingival tissue repair in osteopenic rats. Fifteen female wistar rats were included; in all of them ovariectomy was realized to induce osteopenia; after 45 days, the animals were submitted to 2 surgical techinques 1) dental extraction of the upper central incisor with no socket preservation and 2) 5 mm cranial defect in the calvarium; 5 rats were included in the control group (G1) withput alendronate application; in the group 2 (G2) was used subcutenous alendronate (0.5 mg/kg) once for three weeks and then was realizd the both surgical techniques. In group 3 (G3), after ovariectomy was realized the both dental extraction and the calvarium defect and after that was realized the alendronate protocol. In each group, after six week was realized euthanasia and descriptive histological analysis of the surgical areas involved. In bone formation of the 5 mm cranial defect was observed with good progression in the 3 experimental models and no modification in quality of bone repair was observed. For the gingival tissue in the extraction socket, no differences were observed between G1 and G3. On other hand, in G2 a thinner and reduced gingival epithelium was found. Our results showed that alendronate was not an obstacle for bone repair; deficiencies in re-epithelialization of oral mucosa show the impact of alendronate before dental extraction.

El objetivo fue evaluar la reparación ósea y gingival en ratas con osteopenia. Quince ratas wistar hembras fueron incluidas; en todas ellas se realizo ovarectomia y fue realizada la inducción de osteopenia; después de 45 días, los animales fueron sometidos a dos técnicas quirúrgicas 1) extracciones dentales del incisivo central superior sin preservación alveolar y 2) creación de un defecto craneano de 5 mm en la calota; 5 animales fueron incluidos como grupo control (G1) sin la aplicación de alendronato; en el grupo 2 (G2) se utilizó alendronato subcutáneo (0,5 mg/kg) una vez a la semana durante 3 semanas. En el grupo 3 (G3), después de la ovarectomia se realizó la exodoncia y el defecto en el cráneo y después de ello se inicio el protocolo con alendronato. En cada grupo, después de seis semanas se realizó la eutanasia con descripción histológica de los hallazgos. En el hueso formado en el defecto craneano de 5 mm se observó una adecuada progresión de reparación en los 3 modelos experimentales y no se observó cambios importantes en el modelo de reparación. Para el tejido gingival en el sitio de extracción, no se observaron diferencias entre el grupo G1 y G3. Por otra parte, el G2 presentó un tejido mas delgado con reducción del epitelio gingival; nuestros resultados demuestran que el alendronato no fue un obstáculo en la reparación ósea; deficiencias en la re epitelización de la mucosa oral muestran el impacto del alendronato después de la exodoncia.

Uso de bifosfonatos en pacientes con osteopenia / Biphosphonates in patients with osteopenia

La osteopenia, una disminución de la densidad mineral ósea de menor severidad que la osteoporosis, definida por valores de T-score entre -1,0 y -2,5 en la densitometría ósea , podría asociarse con un mayor riesgo de fracturas. Motivado por el pedido de una paciente con osteopenia que solicita a su médico algún medicamento que le ayude a disminuir su riesgo de fracturas, el autor se pregunta si los bifosfonatos podrían ser beneficiosos para las pacientes con este factor de riesgo. Luego de realizar una búsqueda bibliográfica y seleccionar la evidencia más reciente y de mejor calidad, se concluye que estos fármacos podrían ser útiles para prevenir fracturas en mujeres mayores de 65 años con elevado riesgo de fractura,independientemente del resultado de la densitometría. (AU)

Osteopenia, a minor decrease in bone mineral density, defined by T-score values between -1.0 and -2.5 in a bone densitometry, is associated with an increased risk of fractures. Moved by the request of a patient with osteopenia who asks her doctor for any medication that may help her reduce his risk of fractures, the author wonders if bisphosphonates could be beneficial for patients with this condition. After conducting a bibliographic search and selecting the most recent and best quality evidence, he concluded that these drugs could be useful to prevent fractures in women older than 65 years with ahigh risk of fracture, regardless of densitometry results. (AU)

Efecto del ranelato de estroncio sobre la densidad mineral ósea en hombres con osteoporosis / Effect of strontium ranelate on bone mineral density in men with osteoporosis

La osteoporosis afecta al 6-7% de la población masculina. Es alta la proporción de pacientes con fracturas sin diagnóstico previo de esta enfermedad. La mortalidad luego de una fractura es mayor en hombres que en población femenina; a pesar de esto, la mayoría de los pacientes no reciben tratamiento. Los fármacos aprobados, en nuestro medio, para tratar la osteoporosis masculina son: bifosfonatos, teriparatida y ranelato de estroncio. El objetivo de este estudio fue evaluar el efecto del ranelato de estroncio sobre la densidad mineral ósea en hombres después de 1 año de tratamiento. Se incluyeron los registros de 20 hombres de 67,8±3,0 años, tratados con ranelato de estroncio (2 g/día) durante 1 año. Todos los pacientes presentaban un T-score inferior a -2,5 en cadera o columna vertebral o un T-score inferior a -2,0 y factores de riesgo de fractura. No hubo modificación de parámetros de laboratorio luego del tratamiento (calcemia, calciuria, fósforo sérico, parathormona, 25(OH)vitamina D, fosfatasa alcalina y desoxipiridinolina) en relación a los basales. Luego del tratamiento con ranelato de estroncio se observó incremento de la densidad mineral ósea en columna lumbar: 0,953±0,029 versus 0,997±0,030 g/cm2 (p=0,0068), cuello femoral: 0,734±0,013 versus 0,764±0,016 g/cm2 (p=0,0084) y cadera total: 0,821±0,02 versus 0,834±0,02 g/cm2 (p=0,0419). Conclusión: el tratamiento con ranelato de estroncio produjo un incremento significativo de la densidad mineral ósea en columna lumbar y fémur proximal en hombres con osteoporosis. (AU)

Osteoporosis affects 6-7% of the male population. The proportion of patients with fragility fractures but without diagnosis of the disease is high. Mortality after hip fracture is higher in men than in women; in spite of this, most patients are left without treatment for osteoporosis. Drugs approved, for the treatment of osteoporosis in our country are bisphosphonates, teriparatide, and strontium ranelate (SrR). The objective of this study was to evaluate the effect of SrR on axial BMD in men after one year of treatment. We obtained pertinent data from medical registries of 20 men aged 67,8±3,0 years, treated with oral SrR (2 g/day) for 12 months. All patients had a T-score below -2,5 at the hip or the lumbar spine, or a T-score below -2,0 and one or more risk factors for fracture. The levels of serum calcium, phosphate, alkaline phosphatase, 25-hydroxyvitamin D, or PTH, or urinary calcium and desoxipyridinoline remained unchanged following SrR administration. After treatment with SrR there were significant increases in BMD at the lumbar spine: 0,953±0,029 versus 0,997±0,030 g/cm2 (p=0,0068), femoral neck: 0,734±0,013 versus 0,764±0,016 g/cm2 (p=0.0084), and total hip: 0,821±0,02 versus 0,834±0,02 g/cm2 (p=0,0419). Conclusion: in osteoporotic men, treatment with SrR significantly increases BMD in the lumbar spine and the proximal femur. (AU)

Hepatic Osteodystrophy: The Mechanism of Bone Loss in Hepatocellular Disease and the Effects of Pamidronate Treatment

OBJECTIVES: The present study was designed to evaluate the bone phenotypes and mechanisms involved in bone disorders associated with hepatic osteodystrophy. Hepatocellular disease was induced by carbon tetrachloride (CCl4). In addition, the effects of disodium pamidronate on bone tissue were evaluated. METHODS: The study included 4 groups of 15 mice: a) C = mice subjected to vehicle injections; b) C+P = mice subjected to vehicle and pamidronate injections; c) CCl4+V = mice subjected to CCl4 and vehicle injections; and d) CCl4+P = mice subjected to CCl4 and pamidronate injections. CCl4 or vehicle was administered for 8 weeks, while pamidronate or vehicle was injected at the end of the fourth week. Bone histomorphometry and biomechanical analysis were performed in tibiae, while femora were used for micro-computed tomography and gene expression. RESULTS: CCl4 mice exhibited decreased bone volume/trabecular volume and trabecular numbers, as well as increased trabecular separation, as determined by bone histomorphometry and micro-computed tomography, but these changes were not detected in the group treated with pamidronate. CCl4 mice showed increased numbers of osteoclasts and resorption surface. High serum levels of receptor activator of nuclear factor-κB ligand and the increased expression of tartrate-resistant acid phosphatase in the bones of CCl4 mice supported the enhancement of bone resorption in these mice. CONCLUSION: Taken together, these results suggest that bone resorption is the main mechanism of bone loss in chronic hepatocellular disease in mice.

Incidence of vertebral fractures in calcium and vitamin D-supplemented postmenopausal Brazilian women with osteopenia or osteoporosis: data from Arzoxifene Generations Trial

ABSTRACT Objective Vertebral fracture is the most common osteoporotic fracture, affecting quality of life and increasing mortality. Epidemiological data on incidence of vertebral fracture are scarce in Brazil and throughout Latin America. Our aim was to determine vertebral fracture incidence and risk factors in a female Brazilian population. Subjects and methods Postmenopausal women with low bone mass were studied from the Brazilian placebo group of Arzoxifene Generations Trial (n = 974), followed for up to 5 years. The primary endpoint was new vertebral fractures, detected by X-Ray. Experimental design defined two strata: A. Osteoporosis or previous vertebral fracture with osteopenia; B. Osteopenia without previous fracture. Previous fracture, T-score, ionized calcium, alkaline phosphatase, creatinine and glucose were analyzed at baseline. Crude and adjusted incidence rates of vertebral fractures were estimated and Poisson regression model was used. Results Incidence rate was 7.7 (95% CI of 5.4 to 10.9) per 1,000 person-years (PY), increasing as a function of age. Women with new vertebral fractures had higher prevalence of previous nonvertebral fracture after menopause, were older and had lower lumbar spine (LS) T-score. Fracture risk increased by 46% for each unit reduction in LS T-score. Variables correlated with new vertebral fracture were age (p = 0.034), LS T-score, stratum A (p = 0.001 for both) and previous nonvertebral fracture after menopause (p = 0.019). In the final model, LS T-score was the strongest predictor. Conclusions Incidence rate of vertebral fracture of 7.7 per 1,000 PY. Age and previous fractures were associated with new vertebral fracture, but LS T-score was the most important predictor.

Evaluación del manejo farmacológico de la osteoporosis y la osteopenia en una institución de régimen especial de Bogotá / Pharmacological evaluation of osteoporosis and osteopenia treatment in an institution under the special health system in Bogotá

Objetivo Evaluar los hábitos de prescripción de medicamentos utilizados en el tratamiento de osteoporosis y osteopenia en una institución de salud de régimen especial de Bogotá, comparados guías de manejo internacional de la osteoporosis. Metodología Se realizó un estudio observacional descriptivo de corte transversal con recolección retrospectiva de la información. Corresponde a un estudio de utilización de medicamentos sobre hábitos de prescripción, para el cual se tomó la información de 332 pacientes tratados con Bifosfonatos, sales de calcio, Ranelato de Estroncio y Teriparatida. Se evaluaron los hábitos de prescripción mediante la comparación con las Guías de manejo de la National Osteoporosis Foundation (NOF) y el National Institute for Health and Clinical Excellence (NICE). Resultados El 89 % de la población corresponde a mujeres con un promedio de edad de 67 años. La dosis y frecuencia de administración corresponde a lo establecido por las guías de manejo; el 32,2 % fue tratado con Bisfosfonatos por más de 3 años, el 94,2 % fue tratado en prevención primaria y el 89,6 % fue tratado sin diagnóstico de Osteoporosis mediante Densitometría Mineral Ósea (DMO). De acuerdo a las recomendaciones de la guía NOF el 67,3 % de los pacientes se trató innecesariamente. Conclusiones Los hábitos de prescripción de medicamentos utilizados en el tratamiento de las osteoporosis no están de acuerdo a las guías de manejo, evidenciándose un uso no adecuado especialmente de bifosfonatos.

Objetive To evaluate habits related to the prescription of drugs used in the treatment of osteoporosis and osteopenia in a health institution in Bogota as compared to two international clinical practice guidelines. Methodology An observation and cross-sectional study with retrospective data collection. It is a study of drug-prescribing habits. Information was taken from 331 patients treated with bisphosphonates, calcium salts, strontium ranelate and teriparatide. The prescription habits were assessed by way of a comparison with the NOF clinician's guide for the prevention and treatment of osteoporosis and the National Institute for Health and Clinical Excellence (NICE) guidelines. Results 89 % of the population were women with an average age of 67 years. The dose and frequency of the administration of drugs was in accordance with established guidelines. 32.2 % of patients were treated with bisphosphonates for over 3 years, 94.2% were treated with primary prevention, and 89.6 % had been treated without any osteoporosis diagnosis by DMO. Compared to the NOF guide, 67.3 % of the patients were treated unnecessarily. Conclusions The drug prescription habits used in the treatment of the osteoporosis do not follow the guidelines, showing non-adequate use, especially of bisphosphonates.

Efeitos combinados do ácido zoledrônico e do propranolol sobre a densidade óssea e marcadores bioquímicos de remodelação óssea em ratas osteopênicas submetidas à ovariectomia / Additive effects of zoledronic acid and propranolol on bone density and biochemical markers of bone turnover in osteopenic ovariectomized rats

Objetivos: Este estudo foi desenvolvido para investigar a eficácia e a segurança do ácidozoledrônico (ZOL) e do propranolol (PRO) como monoterapia e terapia combinada em ummodelo de rato com osteoporose pós-menopáusica. Métodos: Ratas Wistar fêmeas foram ovariectomizadas (OVX) ou submetidas à cirurgia simulada (placebo) aos três meses de idade. Doze semanas depois da cirurgia, as ratas foram divididas em seis grupos: (1) placebo + veículo; (2) OVX + veículo; (3) OVX + ZOL (100 µg/kg, dose única intravenosa); (4) OVX + ZOL (50 µg/kg, dose única intravenosa); (5) OVX + PRO (0,1 mg/kg, via subcutânea, cinco dias por semana); (6) OVX + ZOL (50 µg/kg, dose única intravenosa) + PRO (0,1 mg/kg, via subcutânea, cinco dias por semana) durante 12 semanas. Depois do tratamento, testou-se a densidade óssea, a porosidade e a microarquitetura tra-becular dos fêmures. Também foram avaliados marcadores bioquímicos séricos e urinários. Resultados: A terapia combinada com ZOL mais PRO foi mais eficaz em corrigir a diminuição do cálcio sérico e o aumento do nível sérico de fosfatase alcalina e fosfatase ácida resistenteao tartarato do que a monoterapia com ZOL ou PRO. Além disso, a terapia combinada comZOL mais PRO foi mais eficaz em corrigir o aumento dos níveis urinários de cálcio, fósforo ecreatinina do que a monoterapia com ZOL ou PRO. A terapia combinada com ZOL mais PRO também preservou a microarquitetura trabecular e a porosidade do osso cortical. Conclusão: Os resultados sugerem que a terapia combinada com ZOL mais PRO pode ser aabordagem mais eficaz para o tratamento da osteoporose grave em humanos. .

Objectives: The present study was designed to investigate further the efficacy and safety of zoledronic acid (ZOL) and propranolol (PRO) as monotherapy and combination therapy in a rat model of postmenopausal osteoporosis. Methods: Female Wistar rats were ovariectomized (OVX) or sham-operated at 3 months ofage. Twelve weeks post-surgery, rats were randomized into six groups: (1) sham + vehicle; (2) OVX + vehicle; (3) OVX + ZOL (100 뀅g/kg, i.v. single dose); (4) OVX + ZOL (50 뀅g/kg, i.v. single dose); (5) OVX + PRO (0.1 mg/kg, s.c. 5 days per week); (6) OVX + ZOL (50 뀅g/kg, i.v. single dose) + PRO (0.1 mg/kg, s.c. 5 days per week) for 12 weeks. After treatment, femurs were tested for bone density, porosity and trabecular micro-architecture. Biochemical markers in serum and urine were also determined. Results: Combined treatment with ZOL plus PRO corrected the decrease in serum calcium and increase in serum alkaline phosphatase and tartarate resistant acid phosphatase level better than single-drug therapy using ZOL or PRO. Moreover, combined treatment with ZOL plus PRO corrected the increase in urine calcium, phosphorous and creatinine level better than single-drug therapy using ZOL or PRO. Combination therapy using ZOL plus PRO also preserved the trabecular micro-architecture and cortical bone porosity. Conclusion: These data suggest that combined treatment with ZOL plus PRO could be a more effective approach for treating severe osteoporosis in humans. .

The use of bisphosphonates does not contraindicate orthodontic and other types of treatment!

Bisphosphonates have been increasingly used not only to treat bone diseases as well as conditions such as osteopenia and osteoporosis, but also in oncotherapy. The use of bisphosphonates induces clinicians to fear and care. These reactions are associated with controversy resulting from lack of in-depth knowledge on the mechanisms of action as well as lack of a more accurate assessment of side effects. Scientific and clinical knowledge disclosure greatly contributes to professionals' discernment and inner balance, especially orthodontists. Fear does not lead to awareness. For these reasons, we present an article that focuses on that matter. This article was adapted from different journals of different dental specialties, as mentioned on footnote. There is no scientific evidence demonstrating that bisphosphonates are directly involved with etiopathogenic mechanisms of osteonecrosis and jaw osteomyelitis. Their use is contraindicated and limited in cases of dental treatment involving bone tissue. Nevertheless, such fact is based on professional opinion, case reports, and personal experience or experiment trials with failing methods. Additional studies will always be necessary; however, in-depth knowledge on bone biology is of paramount importance to offer an opinion about the clinical use of bisphosphonates and their further implications. Based on bone biopathology, this article aims at contributing to lay the groundwork for this matter.

Cada vez mais se usa os bisfosfonatos nos tratamentos de doenças e de estados ósseos, como a osteopenia e osteoporose, assim como nos protocolos oncoterápicos. O uso dos bisfosfonatos induz muitas reações de medo e cuidado, associadas a polêmicas e controvérsias quase sempre resultantes de uma falta de conhecimento mais profundo dos mecanismos de ação e da falta de uma avaliação mais criteriosa de seus efeitos colaterais. A divulgação e o conhecimento dos aspectos científicos e clínicos contribuem, em muito, para o discernimento e tranquilidade dos profissionais, especialmente dos ortodontistas. O medo não resulta em conscientização. Por essas razões, apresentamos alguns artigos sobre o mesmo assunto, semelhantes e adaptados, em revistas voltadas para as diferentes especialidades odontológicas, entre os quais o citado na nota de rodapé. Nos mecanismos etiopatogênicos da osteonecrose e nas osteomielites, nos maxilares, os bisfosfonatos não se encaixam como um dos fatores diretamente envolvidos e com base em evidências científicas. Suas contraindicações e limitações na prática odontológica como fator limitante de alguns tratamentos envolvendo o tecido ósseo estão baseadas, principalmente, em opiniões, casos clínicos e na experiência pessoal ou trabalhos experimentais com algumas falhas nos métodos experimentais. Sempre serão necessários mais estudos, mas um cuidado importante é se aprofundar no conhecimento da biologia óssea para, quando necessário, emitir-se opiniões sobre protocolos de conduta na clínica odontológica quanto ao uso bisfosfonatos e suas implicações. Esse artigo objetiva contribuir na fundamentação de abordagens sobre esse assunto a partir da biopatologia óssea.

[Effects of calcitonin nasal spray on serum bone resorptive marker CTX and other laboratory findings in osteopenic menopausal women: a clinical trial]

Various therapeutic options such as calcitonin have been suggested for patients with low bone density, despite uncertain efficacy in most patients. C-telopeptide of type I collagen [CTX] is a new bone marker used for the assessment of bone resorption. The aim of this study was to evaluate the therapeutic effects of nasal spray calcitonin in women with osteopenia via serum CTX and other laboratory tests. We conducted a self controlled clinical trial in 2009 on 105 women of menopausal age diagnosed in Baqiyatallah Hospital Clinic with osteopenia based on a bone mineral density score of 1.5 SD lower than peak bone mass. The patients were assigned to receive nasal spray calcitonin [200 IU/day], calcium [1000 mg/day] and Vit-D [400 IU/day] for 6 months. Serum CTX and other laboratory parameters were measured before and after the treatment. The data were analyzed by SPSS, version 17, using t-tests and a P<0.05 was considered statistically significant. Fifty-two patients completed the study and the mean CTX level decreased significantly from 3.10 +/- 2.03 to 2.61 +/- 1.82 pmol/lit [P<0.001], but total serum levels of PTH, Ca, AST, ALT and Alkaline Ph decreased insignificantly. It seems that nasal spray of calcitonin is significantly effective in preventing disease progression and treatment of low bone density by inhibiting bone tissue resorption indicated by CTX although further studies with larger samples sizes and inclusion of control groups are warranted

Bisphosphonates in the treatment of metabolic bone diseases / Atualização sobre bisfosfonatos nas doenças osteometabólicas

Osteoporosis is a disease characterized by low bone mass associated with the deterioration of microarchitecture, due to an imbalance either in high bone resorption or low bone formation or in both, leading to a high risk of fractures. Bisphosphonates are medications which reduce the ability of osteoclasts to induce bone resorption and consequently improve the balance between resorption and formation. There are bisphosphonates approved for the prevention and treatment of osteoporosis. Administration can be oral (daily, weekly or monthly) or intravenous (quarterly or yearly). These medications are well tolerated and with the correct instructions of administration have a good safety profile. Serious side effects, such as, osteonecrosis of jaw is very rare. Bisphosphonates are the most prescribed medication for the treatment of osteoporosis.

Osteoporose é uma doença caracterizada por baixa massa óssea associada à deterioração da microarquitetura devido ao desbalanço pela alta reabsorção, baixa formação ou ambas, levando a um alto risco de fraturas. Bisfosfonatos são medicamentos que reduzem a capacidade de os osteoclastos induzirem a reabsorção óssea e, consequentemente, melhorar o balanço entre reabsorção e formação. Há bisfosfonatos aprovados para prevenção e tratamento da osteoporose. A administração pode ser via oral (diária, semanal ou mensal) ou intravenosa (trimestral ou anual). Essas medicações são bem toleradas e, seguindo as recomendações adequadas, apresentam alto grau de perfil de segurança. Efeitos colaterais sérios, como osteonecrose de mandíbula, são raros. Bisfosfonatos são as medicações mais prescritas para o tratamento da osteoporose.

Comparison of the Effects of Alendronate and Alfacalcidol on Hip Bone Mineral Density and Bone Turnover in Japanese Men Having Osteoporosis or Osteopenia with Clinical Risk Factors for Fractures

PURPOSE: The comparative effects of alendronate and alfacalcidol on bone mineral density (BMD) and bone turnover have already been established in postmenopausal women with osteoporosis. An open-labeled prospective study was conducted to compare the treatment effects of alendronate and alfacalcidol on hip BMD and bone turnover in Japanese men with osteoporosis or osteopenia with clinical risk factors for fractures. MATERIALS AND METHODS: One hundred twelve men with osteoporosis or osteopenia with clinical risk factors for fractures (mean age: 71.4 years) were randomly divided into two groups of 56 patients each: the alendronate (5 mg daily) and alfacalcidol (1 microgram daily) groups. The BMD of the total hip, urinary level of cross-linked N-terminal telopeptides of type I collagen (NTX), and serum levels of bone-specific alkaline phosphatase (BSAP) were measured during the 12-month-treatment period. RESULTS: Forty-five patients in the alendronate group and 42 patients in the alfacalcidol group completed the trial. Alendronate increased BMD (+2.3% at 12 months) following reductions in the urinary level of NTX (-46.4% at 3 months) and serum level of BSAP (-34.1% at 12 months), while alfacalcidol sustained BMD (-1.9% at 12 months) as well as the urinary level of NTX (+13.2% at 3 months) and serum level of BSAP (+1.8% at 12 months). CONCLUSION: The present study confirmed that alendronate has better efficacy than alfacalcidol (active control) in increasing hip BMD and reducing bone turnover in Japanese men with osteoporosis or osteopenia with clinical risk factors for fractures.

Comparison of the Effects of Alendronate and Alfacalcidol on Hip Bone Mineral Density and Bone Turnover in Japanese Men Having Osteoporosis or Osteopenia with Clinical Risk Factors for Fractures

PURPOSE: The comparative effects of alendronate and alfacalcidol on bone mineral density (BMD) and bone turnover have already been established in postmenopausal women with osteoporosis. An open-labeled prospective study was conducted to compare the treatment effects of alendronate and alfacalcidol on hip BMD and bone turnover in Japanese men with osteoporosis or osteopenia with clinical risk factors for fractures. MATERIALS AND METHODS: One hundred twelve men with osteoporosis or osteopenia with clinical risk factors for fractures (mean age: 71.4 years) were randomly divided into two groups of 56 patients each: the alendronate (5 mg daily) and alfacalcidol (1 microgram daily) groups. The BMD of the total hip, urinary level of cross-linked N-terminal telopeptides of type I collagen (NTX), and serum levels of bone-specific alkaline phosphatase (BSAP) were measured during the 12-month-treatment period. RESULTS: Forty-five patients in the alendronate group and 42 patients in the alfacalcidol group completed the trial. Alendronate increased BMD (+2.3% at 12 months) following reductions in the urinary level of NTX (-46.4% at 3 months) and serum level of BSAP (-34.1% at 12 months), while alfacalcidol sustained BMD (-1.9% at 12 months) as well as the urinary level of NTX (+13.2% at 3 months) and serum level of BSAP (+1.8% at 12 months). CONCLUSION: The present study confirmed that alendronate has better efficacy than alfacalcidol (active control) in increasing hip BMD and reducing bone turnover in Japanese men with osteoporosis or osteopenia with clinical risk factors for fractures.

Histomorfometria óssea de ratas hipertireóideas lactantes e não-lactantes / Bone histomorphometry of lactating and no lactating hyperthyroid rats

O objetivo deste estudo foi verificar se o hipertireoidismo potencializa a osteopenia causada pela lactação. Foram utilizadas 24 ratas adultas distribuídas em quatro grupos: eutireóideo não lactante (controle), eutireóideo lactante, hipertireóideo não-lactante e hipertireóideo lactante. Todos os animais foram necropsiados, 20 dias após a gestação. As vértebras torácicas e lombares, o fêmur e a tíbia foram colhidos, descalcificados e submetidos à análise histomorfométrica. O grupo eutireóideo lactante apresentou osteopenia intensa em todos os sítios ósseos estudados. No grupo hipertireóideo não-lactante, não houve alteração da porcentagem de tecido ósseo trabecular nos sítios analisados. No grupo hipertireóideo lactante, havia osteopenia na tíbia e no fêmur, semelhante à do grupo eutireóideo lactante. Mas a porcentagem de tecido ósseo trabecular em todos os corpos vertebrais foi significativamente maior em comparação ao grupo eutireóideo lactante. Conclui-se que o hipertireoidismo não agrava a osteopenia lactacional em ratas, mas minimiza a osteopenia vertebral por estimular a atividade osteoblástica.

The objective of this study was to verify if hyperthyroidism potentiates the osteopenia lactational. 24 adult female rats were distributed in four groups: euthyroid no lactating (control), euthyroid lactating, hyperthyroid no lactating and hyperthyroid lactating. 20 days after gestation, all the animals were necropsied. The thoracic and lumbar vertebrae, the femur and tibia were decalcified and processed for histomorphometric analysis. The euthyroid lactating group presented intense osteopenia in the studied bones. In the hyperthyroid no lactating group, there was not any change in trabecular bone percentage in none of the analyzed bone. In the hyperthyroid lactating group, there was osteopenia in the tibia and femur, similar to the one in the euthyroid lactating group. But the trabecular bone percentage in all the vertebral bodies was significantly larger in comparison with the euthyroid lactating group. It was concluded that the hyperthyroidism does not potentiate the osteopenia lactational in female rats, but it minimizes the vertebral osteopenia once it stimulates the osteoblastic activity.

Ranelato de estroncio y masa ósea maxilar. Reporte de investigación clínica: prueba piloto / Strontium ranelate and jaw bone mass. Report of clinical research: a pilot study

Con la finalidad de evaluar la efectividad del ranelato de estroncio Protos(R) 2 gr en osteopenias maxilares focalizadas, son estudiados 5 pacientes con estas características, por medio de pQCT. Durante seis meses reciben 2 gramos diarios de ranelato de estroncio. Concluido este lapso son medidas las áreas ROls (región ósea de interés), discriminando entre valores de cortical interna externa y trabecular. Son comparadas los ROIs en lo que a densidad volumétrica y superficie de area, y se expresan los resultados estadísticamente. El resultado expresa un aumento en la masa de hueso tipo II y III y principalmente la de tipo III, encontrándose un descenso en la masa de tipo IV, hueso de mala calidad biomecánica, permaneciendo el hueso de tipo I, que es el hueso cortical, sin variación. Estos resultados abren la posibilidad de realizar un estudio más amplio con la finalidad de confirmar fehacientemente los beneficios de esta medicación para uso del odontólogo.

Uso de bifosfonatos em crianças e adolescenes / Use of bisphophonates in children and adolescents

Os bifofonatos são os medicamentos mais amplamente utilizados no tratamento de doenças associadas ao aumento de reabsorção óssea em adulto, incluindo a osteoporose pós-menopausa (indicação mais frequente), a doença de Paget e metástases ósseas. Os bifofonatos têm sido usados com bons resultados em crianças e pouco ou nenhum efeito colateral em várias doenças: osteogênese imperfeita, osteoporose induzida por corticóide, idiopática juvenil e por desuso, doença óssea metabólica, calcificação heterotópica de tecidoas moles, hipercalcemia resistente, hipervitaminose D e displasia fibrosa (DF) da síndrome de Mc-Cune Albright (SMA). Os melhores resultados são descritos nas crianças portadoras de osteogênese imperfeita, DFO da SMA e osteoporose induzida por corticóides. Os bifofonatos são análogos sintéticos estáveis no pirofosfato que inibem o crescimento e a dissolução dos cristais de hidroxiapatita do osso a partir da redução da atividade osteoclástica. Nos tecidos, promovem supressão do turnover ósseo, evidenciada no exame histológico e histomorfométrico. Durante seu uso ocorre aumento da densidade óssea devido à diminuição da taxa de iniciação de novos ciclos de remodelagem e consequente redução dos espaços de remodelamento ósseo. Emboram existam questionamentos sobre possíveis efeitos adversos no esqueleto em crescimento e na qualidade do osso formado a longo prazo, os bons resultados descritos são encorajadores e os efeitos colaterais bem tolerados.

randomized clinical trial of prophylactic effects of vitamin D on difrent indices of osteopenia of prematurity

Prevention and treatment of the rickets of prematurity is an important aspect of the care of preterm infants. The purpose of this study was to compare the prophylactic effects of different doses of vitamin D on the clinical, biochemical and radiological indices of the rickets of prematurity. In a randomized clinical trial, 68 premature infants [<38 weeks] with birth weight under 2000 g, randomly divided in two groups. Infants received 400 IU/d vitamin D in Group A [n=32] and 1000 IU/d in group B [n= 36]. On the 9th week of birth, serum calcium, phosphate, and alkaline phosphatase were measured and x-ray of left wrist and physical examination were performed. The average serum calcium, phosphate and alkaline phosphatase in both groups had no difference [P= 0.326, 0.466, 0.147, respectively] and no one had a radiological or clinical picture of rickets. In conclusion we recommend low dose vitamin D for prevention of the osteopenia of prematurity

Trastornos de la conducta alimentaria como factor de riesgo para osteoporosis / Eating disorders as risk factors for osteoporosis

Los trastornos de la conducta alimentaria son comunes en mujeres jóvenes con una prevalencia estimada de entre 4-5 por ciento. La pérdida de masa ósea es una complicación física de la anorexia nervosa y trastorno alimentario no especificado que afecta tanto a hueso cortical como trabecular. El efecto sinérgico de la desnutrición y la deficiencia de estrógenos produce una pérdida de masa ósea a través del desacoplamiento entre resorción osteoclástica y formación osteoblástica. La severidad varía dependiendo de la duración de la enfermedad, el peso menor alcanzado y la actividad física. La repercusión a largo plazo es evidente pues existe un incremento en el riesgo de fractura en las pacientes que han padecido anorexia nervosa. La primera línea de tratamiento para recuperar la masa ósea es la rehabilitación nutricia y un incremento de peso. La terapia de reemplazo hormonal podría ser efectiva si se combina con métodos anabólicos. Los términos osteopenia y osteoporosis fueron adoptados para definir la deficiencia de masa ósea en adultos. Los autores de las publicaciones que fueron revisadas utilizaron dichos términos para definir datos densitométricos en sujetos jóvenes que no han alcanzado la masa ósea pico. Sugerimos el término "hipo-osteogenesia" para definir el desarrollo deficiente de masa ósea en adolescentes o niños.

Tratamiento de la Osteoporosis

La osteoporosis es el síndrome más frecuente dentro de la enfermedad metabólica ósea. Su importancia aumenta de forma paralela al aumento de la esperanza de vida de la población y al envejecimieto de ésta; su complicación, la fractura, puede producir un enmpeoramiento severo de la calidad de vida, siendo la de cadera una causa importante de mortalidad en los ancianos. Al diagnosticar la existencia de la osteoporosis es importante caracterizar su etiología y grado de recambio óseo para iniciar el tratamiento, el cual puede dividirse en profiláctico y terapéutico sidno su objetivo final la prevención de complicaciones.Son múltiples los tratamiento propuestos para este proceso, apareciendo cada año nuevos fármacos. Los tratamientos tienden a mantener al paciente con niveles de densidad mineral ósea por encima del riesgo de fracturas, pero debido a que la pérdida de calcio es un fenómeno fisiológico, una vez se suspende el tratamiento, este proceso de pérdida se inicia de nuevo. La elección del fármaco será individualizada, deberá basarse en el tipo de osteoporosis, su remodelado óseo y la tolerancia y respuesta del paciente al fármaco