Efectos de la administración local de PTH 1-34 a bajas dosis en un modelo experimental de periodontitis: estudio piloto / Local effects of low dose of PTH 1-34 on experimental periodontitis: pilot study

La periodontitis es una patología inflamatoria que aumenta la resorción de hueso alveolar (HA), pérdida de la inserción dentaria y posible exfoliación. Evaluamos el efecto de la administración intermitente de bajas dosis de parathormona (PTH) 1-34 sobre la recuperación de la masa ósea pérdida en un modelo experimental de periodontitis inducida por una ligadura periodontal (LP) con hilo de algodón alrededor de la pieza dentaria. Las ratas fueron divididas luego de 5 días en instaurada la periodontitis en: CT LP sin trata-miento y PTH LP tratados con 0,2 µg/kg PTH 1-34 subcutánea local, tres veces por semana por 17 días. El control absoluto fue un tercer grupo sin LP (CT). Se estudiaron parámetros antropométricos, bioquímicos e histomosfométricos en tibias y hemimandibulas. La calcemia, fosfatemia, CTX sérico, PTHi y vo-lumen óseo (BV/TV%) de tibias fueron similares en los tres grupos. El BV/TV% del HA fue significativamente menor en PTH LP respecto de CT pero mayor que CT LP (p<0.05). La pérdida ósea de HA porcentual fue significativamente mayor en CT LP (p<0.05). La altura del ligamento periodontal fue significativamente menor en PTH LP que en CT (p<0.05) y mayor respecto de CT LP, sin alcanzar diferencias significativas. Los resultados del presente estudio piloto sugieren que la administración intermitente de PTH en bajas dosis y durante un periodo de tiempo corto disminuye la progresión de la enfermedad periodontal sin generar efectos sistémicos. Como no se logró regenerar totalmente el tejido periodontal se requieren estudios adicionales. (AU)

Periodontitis is an inflammatory chronic disease with high prevalence in adults that induces a progressive alveolar bone (AB) loss leading to tooth loss. Experimental periodontitis can be induced in rats by cotton ligature placement (LP) in the gingival sulcus around the molar teeth. The biofilm accumulation and disruption of the gingival epithelium lead to bone resorption. We investigated whether intermittent administration of a low dose of PTH 1-34 may recover the alveolar bone loss in the experimental periodontitis induced in female Wistar rats. Animals were randomly divided in two groups which were subcutaneously injected with: saline solution (CT LP) or 0,2 µg/kg PTH 1-34 (PTH LP) three times per week during 17 days. Unligated rats were taken as healthy controls (CT). Anthropometric, biochemical and histologic analysis of tibia and hemimandible were done. No differences in serum calcium, phosphorus, CTX, PTHi or subchondral tibia bone volume (BV/TV%) were observed between the three groups. AB BV/TV% was significantly lower in PTH LP than in CT but higher than in CT LP (p<0.05). The highest percentage of AB loss was observed in CT LP. The height of periodontal ligament was lower in PTH LP than in CT (p<0.05) but not significantly higher than CT LP.The increase in AB loss by experimental periodontitis appears to be corrected by the intermittent administration of low doses of PTH without systemic effect. As the recovery of periodontal tissue was only partial, additional studies should be done.

Osteoactivos en insuficiencia renal crónica avanzada: a propósito de un caso / Osteoactive in advanced chronic renal failure: a case report

El propósito de la terapia en el desorden del metabolismo óseo mineral asociado a la enfermedad renal crónica (IRC) consiste en restaurar el balance mineral, y, en la osteoporosis, mantener o aumentar la masa ósea. Ambas terapias tratan de evitar la fractura ósea. La mayoría de los osteoactivos están contraindicados en la insuficiencia renal crónica avanzada (estadios 4 y 5), y las terapias son empíricas. Algunos autores opinan que sin anomalías bioquímicas del desorden del metabolismo óseo mineral asociado a la enfermedad renal crónica avanzada se podría intentar el tratamiento estándar para la osteoporosis. Antes de intentar la terapia osteoactiva se debe corregir el desorden mineral óseo que pudiera presentarse asociado a la IRC, y en la indicación del tipo de osteoactivo se sugiere seleccionar al paciente según su estado óseo. Se aconseja que la administración de los antirresortivos se realice a dosis menores con respecto a los que tienen mejor función renal junto con aportes adecuados de calcio y vitamina D, antes y durante el tratamiento para prevenir el riesgo de severas hipocalcemias y un efecto óseo excesivo. Se presenta el caso clínico de una mujer de 65 años, con diagnóstico de osteoporosis de etiología multifactorial, fractura de pelvis, múltiples fracturas vertebrales e insuficiencia renal crónica avanzada, entre otras comorbilidades, y probable enfermedad ósea adinámica. Recibió inicialmente terapia con teriparatide y luego con denosumab, complicándose con hipocalcemia asintomática. (AU)

The purpose of therapy for the bone mineral metabolism disorder associated with chronic kidney disease is to restore the mineral balance; and to maintain or increase bone mass in osteoporosis. The goal of both types of therapy is to avoid bone fractures. Most antiosteoporotic drugs are contraindicated in advanced chronic renal failure (CRF) stages 4 and 5, and the therapies are empirical. Some authors believe that without biochemical abnormalities of the mineral bone metabolism disorder associated with advanced chronic kidney disease, standard treatment for osteoporosis could be attempted. Before attempting antiosteoporotic therapy, the bone mineral disorder that may be associated with CRF must be corrected, and in the indication of the type drug it is suggested that the patient be selected according to their bone status. It is advised that the administration of anti-resorptives be performed at lower doses in individuals with poor renal function compared to those with better renal function together with adequate calcium and vitamin D, before and during treatment to prevent the risk of severe hypocalcemia, and an excessive bone effect. We present the clinical case of a 65-year-old woman with a diagnosis of osteoporosis of multifactorial etiology, pelvic fracture, multiple vertebral fractures and advanced chronic renal failure, among other comorbidities and probable adynamic bone disease. The patient received initial therapy with teriparatide and followed by denosumab administration and exhibited asymptomatic hypocalcemia. (AU)

Guías para el diagnóstico, la prevención y el tratamiento de la osteoporosis inducida por glucocorticoides en el adulto / Guidelines for the diagnosis, prevention and treatment of glucocorticoid-induced osteoporosis in adults

La osteoporosis inducida por glucocorticoides (OIC) es la causa más común de osteoporosis secundaria. La pérdida ósea se produce en forma temprana, en los primeros meses siguientes a la introducción de los glucocorticoides (GC), dependiendo de la dosis diaria. La patogénesis es multifactorial y el principal efecto deletéreo es la inhibición de la formación ósea. Los GC inducen fracturas por fragilidad ósea, especialmente en la columna vertebral, y esto genera incapacidad funcional. En los últimos años se han publicado algunas guías internacionales elaboradas por consenso para la prevención y el tratamiento de la OIC. La Sociedad Argentina de Osteoporosis designó a un grupo de trabajo para elaborar una guía propia y actualizada para el diagnóstico, la prevención y el tratamiento de la OIC (GE-OIC-SAO). (AU)

Glucocorticoid-induced osteoporosis (GIO) is the most common cause of secondary osteoporosis. It occurs early, with rapid bone loss in the first few weeks after the initiation of the treatment, with a rate that is dependent mainly on the daily dose. While the pathogenesis is multifactorial, the highest inhibitory effect occurs on bone formation. Glucocorticoids induce fragility fractures, especially in spine, generating functional disability. In recent years, there have been some international guidelines developed by consensus for the prevention and treatment of GIO. The Argentinean Osteoporosis Society appointed a working group to prepare a national guide updating the diagnosis, prevention and treatment of GIO. (AU)

Utilidad del tratamiento secuencial con teriparatide y denosumab en la osteoporosis de alto riesgo: nuestra experiencia asistencial / Benefits of sequential treatment of high risk osteoporosis with teripartide and denosumab: our experience

El tratamiento de las formas graves de osteoporosis representa un desafío en la práctica asistencial. Reportamos tres pacientes con formas graves de osteoporosis tratadas en el Instituto de Diagnóstico e Investigaciones Metabólicas con un esquema secuencial de teriparatide 20 µg/día durante 18 meses, seguidos de 12 meses de denosumab 60 mg semestral. Luego de 18 meses de tratamiento con teriparatide la densidad mineral ósea en columna aumentó 5,86±1,01% y en cuello femoral 1,92±3,10%; al finalizar los doce meses de tratamiento con denosumab se constató un aumento total en columna de 10,45±1,70% y en cuello femoral 9,28±3,86%. El tratamiento con teriparatide se acompañó de un aumento en los niveles plasmáticos de telopéptidos del colágeno óseo (CTX) y en el período de tratamiento con denosumab dichos valores disminuyeron de manera significativa, mostrando el impacto de estos fármacos sobre el remodelado óseo. Concluimos que el tratamiento secuencial con teriparatide y denosumab en dosis convencionales resultó beneficioso en las tres pacientes tratadas. Sería de utilidad ampliar esta experiencia en un trabajo prospectivo. (AU)

High risk osteoporosis treatment is a challenge in daily medical practice. We report three patients that attended our institution with severe osteoporosis who received sequentially teriparatide (20 ug daily) for eighteen months followed by denosumab (60 mg every six months) for twelve months. After teriparatide treatment bone mineral density increased 5.86±1.01% at lumbar spine and 1.92±3.10 % at femoral neck, while after denosumab it continued increasing to reach a total of 10.45±1.70% at lumbar spine and 9.28±3.86% at femoral neck. Teriparatide treatment increased bone resorption evidenced by high serum CTX while after denosumab it fell abruptly, showing the impact of these two drugs on bone turnover. We conclude that sequential treatment with teriparatide and denosumab in approved doses was beneficial for these three patients. Prospective studies are needed. (AU)

At Least One Cyclic Teriparatide Administration Can Be Helpful to Delay Initial Onset of a New Osteoporotic Vertebral Compression Fracture

PURPOSE: Teriparatide markedly increases bone formation and strength, while reducing the incidence of new-onset osteoporotic vertebral compression fractures (OVCFs). In some countries, expenses for teriparatide use are covered by medical insurance for up to 6 months; however, the national medical insurance of the authors' country does not cover these expenses. This retrospective cohort study compared the therapeutic effects of teriparatide on the initial onset of a new OVCF after treatment of osteoporosis and/or related OVCFs with regard to therapeutic durations of longer than 3 months (LT3M) or shorter than 3 months (ST3M). MATERIALS AND METHODS: From May 2007 to February 2012, 404 patients who were prescribed and administered teriparatide and who could be followed-up for longer than 12 months were enrolled. They were divided into two groups depending on teriparatide duration: LT3M (n=132) and ST3M (n=272). RESULTS: The group with the teriparatide duration of LT3M showed significantly less development of an initial OVCF within 1 year (p=0.004, chi-square). Duration of teriparatide use, body mass index, pre-teriparatide lowest spinal bone mineral density, and severity of osteoporosis significantly affected multiple regression analysis results (p<0.05). Survival analysis of first new-onset OVCFs demonstrated a significantly better survival rate for the LT3M group (log rank, p=0.005). Also, the ST3M group showed a higher odds ratio of 54.00 for development of an initial OVCF during follow-up than the LT3M group (Mantel-Haenzel common odds ratio, p=0.006). CONCLUSION: At least one cyclic teriparatide administration is recommended to provide a protective effect against the initial onset of a new OVCF for up to one year after therapy.

Efficacy of teriparatide in increasing bone mineral density in postmenopausal women with osteoporosis--an Indian experience.

BACKGROUND AND OBJECTIVE: Osteoporosis is emerging as a leading cause of substantial morbidity in India, particularly in postmenopausal women. Teriparatide (recombinant human parathyroid hormone [1-34]) increases bone formation and improves bone microarchitecture, thereby reducing the risk of fractures. This study was conducted to evaluate the efficacy of teriparatide in increasing bone mineral density (BMD) in postmenopausal women with osteoporosis. MATERIAL AND METHODS: A randomised, prospective, multicentre, open-label, controlled study was conducted on 82 postmenopausal women with established osteoporosis. Patients were randomly divided into control and teriparatide groups, each group consisting of 41 patients. All the patients were supplemented with 1000 mg of elemental calcium and 500 IU of vitamin D throughout the study period of 180 days. Besides, teriparatide group patients were administered teriparatide 20 microg daily subcutaneously. Lumbar spine, femoral neck and total hip BMD, bone mineral content (BMC) and bone area were measured by dual energy x-ray absorptiometry (DXA) at baseline and at the end of 6 months of treatment. Bone biomarkers, such as serum bone specific alkaline phosphatase (BSAP) and serum osteocalcin (OC), representing bone formation, and urinary deoxypyridinoline (DPD), representing bone resorption were assessed at baseline, and at 3 and 6 months of treatment. RESULTS: During the study period, 9 patients (11%) were lost to follow-up--6 in control group (7.3%) and 3 in teriparatide group (3.7%). There was an excellent compliance to both oral and injectable medication. The investigational product teriparatide was well tolerated and there were no serious adverse events. In addition, there were no significant differences between the groups in the incidence of adverse events. The percentage of increase in lumbar spine BMD, which is the primary endpoint, was significantly (P < 0.001) higher in teriparatide group compared to that in control group (6.58% vs. 1.06%). Further, teriparatide significantly increased percentage of change in lumbar spine T-score (P < 0.001), BMC (P < 0.001) and bone area (P < 0.028) compared to control group at 6 months. Administration of teriparatide resulted in a significant percentage of increase in all the bone biomarkers in teriparatide group compared to control group patients at 3 and 6 months over baseline, thereby showing that there was a significant increase in bone turnover in teriparatide group of patients. CONCLUSION: These results show that teriparatide is an effective and safe drug in increasing the BMD and therefore, teriparatide provides yet another new therapeutic option for reducing the risk management of osteoporosis in postmenopausal women (clinicaltrials.gov number, NCT00500409).