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)

[Reduction in requirements of oral calcium and 1-25 dihydroxy vitamin D in patients with post-surgical hypoparathyroidism treated with teriparatide (PTH1-34)]. / Reducción en los requerimientos de calcio oral y de 1-25 dihidroxi-vitamina D en pacientes con hipoparatiroidismo posquirúrgico tratados con teriparatida (PTH1-34).

The objective of the study is to evaluate the effect of daily administration of recombinant parathyroid hormone (PTH1-34), 20 µg, on serum calcium concentrations (Cas), and the requirements of oral calcium and calcitriol in patients with hypoparathyroidism. It is a prospective, longitudinal study, analytical, with intervention, in patients treated with high doses of calcium (> 7 g/day), with symptoms of hypocalcemia and/or intolerant to treatment. Serum levels of phosphorus (Ps) and Cas, urinary calcium excretion, oral doses of calcitriol and calcium were compared before and after administration of teriparatide, for three months on average, in patients with post-surgical hypoparathyroidism. We studied 16 patients with oral elemental calcium requirements of 22.5 ± 16 g/day of calcitriol 0.79 ± 0.4 µg/day. Cas at baseline was 7.6 ± 1.2 and Ps 5.4 ± 0.76 mg/dl. After administration of teriparatide, Cas was 9.0 ± 0.69 mg/dl (p = 0.007) and Ps of 4.5 ± 0.87 mg/dl (p = 0.003). Doses of calcium and calcitriol showed a statistically significant reduction (p = 0.0001 and 0.001, respectively). We conclude that use of recombinant parathyroid hormone can normalize Cas and Ps, with reduction in oral calcium and calcitriol requirements.

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)

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)

Effect of teriparatide on induced tooth displacement in ovariectomized rats: a histomorphometric analysis.

INTRODUCTION: The aim of this study was to evaluate morphologically the effect of teriparatide on induced orthodontic movement of the maxillary first molars in ovariectomized rats. METHODS: Ovariectomized Wistar rats (n = 16), ovariectomized rats treated with teriparatide (n = 16), and nonovariectomized rats (n = 16) had orthodontic tooth movement for 5 and 7 days. The group treated with teriparatide received a subcutaneous injection (Forteo, Eli Lilly, Indianapolis, Ind; 30 µg/kg/day) for 90 days after the ovariectomy. Histologic sections obtained from the maxilla were prepared for the morphometric analysis of dental movement, the thickness of the periodontal ligament, and the number of osteoclasts in the pressure and tension areas of the apex of the root and alveolar crest in the distal root of the maxillary first molars. RESULTS: The ovariectomized rats treated with teriparatide had similar responses at 5 and 7 days after the induced dental movements compared with the untreated ovariectomized group. Both ovariectomized groups had greater molar movement on day 7 day compared with the controls (P <0.05). There were no statistically significant differences between groups in the spacing of the periodontal ligament or the number of osteoclasts in the areas studied. CONCLUSIONS: These data suggest that the treatment of osteoporosis with teriparatide is a good alternative for patients undergoing orthodontic treatment.

Effect of systemic intermittent administration of human parathyroid hormone (rhPTH[1-34]) on the resistance to reverse torque in rabbit tibiae.

The aim of this study was to evaluate the effect of intermittent administration of human parathyroid hormone [rhPTH (1-34)] on the removal torque of implants placed in rabbit tibiae. Twenty male New Zealand rabbits were submitted to implant surgery. Each animal received one machined screw-type implant (3.75 mm diameter x 8 mm length) in the proximal metaphysis of the right tibia. The rabbits were then divided into 2 groups: the test group (n = 10) received 6 microg/kg of rhPTH (1-34) subcutaneously in the dorsal region 3 days a week, and the control group (n = 10) received placebo. Removal torque was performed at 28 and 56 days after implant placement for both groups. The mean removal torque values at 28 days were 37.0 +/- 4.36 Ncm and 47.4 +/- 6.77 Ncm for control and test groups respectively (P < .05). At 56 days the reverse torque was 45.8 +/- 3.96 Ncm for the control group and 55.8 +/- 2.86 Ncm for the test group, indicating that the removal torque was significantly higher in the test groups (P < .05). These results demonstrated that intermittent treatment with rhPTH (1-34) enhanced the removal torque of implants in rabbit tibiae.