Clinical features, diagnostic evaluation and responses to treatment in Paget's disease of bone in a center specialized in bone metabolism / Características clínicas, evaluación diagnóstica y respuestas al tratamiento de la enfermedad de Paget ósea en un centro especializado en metabolismo óseo

Abstract The epidemiology of Paget's disease of bone (PDB) has changed in the last years but there is no update data on its clinical presentation, diagnosis and management in Latin America. Our aim was to describe its clinical features, diagnostic evaluation and responses to treatment in a group of PDB patients treated between June 2012 and December 2019 in an institution specialized in bone diseases, in Buenos Aires, Argentina. The frequency of PDB (180/10 714) was 1.68%. Median age was 67 (range 39-97) years and 59.5% were women. Most patients were asymptomatic (58.6%) and had monostotic disease (54.3%). Favorable responses were obtained in all patients who were treated with zoledronate (n = 36), in 10 out of 14 treated with pamidronate, in 9 out of 10 who received intravenous ibandronate and in 12 out of 13 who received oral bisphosphonates. The response rates were not significantly different when we compared monostotic vs. polyostotic disease. Among the biochemical parameters, mean values of bone specific and total alkaline phosphatase, and C-terminal cross-linked telopeptide of type I collagen decreased significantly after treatment with bisphosphonates. It seems that our results reflect the change in PDB epidemiology towards a more indolent disease. In the future, this would probably allow physicians to use lower doses of bisphosphonates than the ones historically recommended for these patients.

Resumen La epidemiología de la en fermedad de Paget ósea (EPO) ha cambiado en los últimos años. Son necesarios datos actualizados sobre su forma de presentación clínica, diagnóstico y tratamiento en nuestra región. Nuestro objetivo fue describir las características clínicas, evaluación diagnóstica y respuestas al tratamiento de un grupo de pacientes con EPO en un centro especializado en salud ósea de Buenos Aires, Argentina. Se evaluaron todos los pacientes que fueron atendidos en nuestra institución por enfermedades óseas entre junio de 2012 y diciembre de 2019. La frecuencia de EPO (180/10 714) fue de 1.68%. La mediana de edad fue de 67 (rango 39-97) años. El 59.5% eran mujeres. La mayoría se encontraba asintomático (58.6%) y tenían enfermedad monostótica (54.3%). Se objetivaron respuestas favorables en todos los que recibieron zoledronato (n = 36), en 10 de 14 pacientes que recibieron pamidronato, en 9 de 10 que utilizaron ibandronato endovenoso y en 12 de 13 con bifosfonatos orales. Los porcentajes de respuesta no variaron significativamente entre pacientes con formas monostóticas y poliostóticas. Entre los parámetros bioquímicos, los valores de fosfatasa alcalina total y ósea y de β cross-laps disminuyeron significativamente luego del tratamiento con bifosfonatos. Nuestros resultados reflejarían un cambio en la epidemiología de la EPO hacia una forma de presentación más indolente. Esto permitiría probablemente el uso de dosis más bajas de bifosfonatos que las históricamente recomendadas para estos pacientes.

Clinical features, diagnostic evaluation and responses to treatment in Paget's disease of bone in a center specialized in bone metabolism.

The epidemiology of Paget's disease of bone (PDB) has changed in the last years but there is no update data on its clinical presentation, diagnosis and management in Latin America. Our aim was to describe its clinical features, diagnostic evaluation and responses to treatment in a group of PDB patients treated between June 2012 and December 2019 in an institution specialized in bone diseases, in Buenos Aires, Argentina. The frequency of PDB (180/10 714) was 1.68%. Median age was 67 (range 39-97) years and 59.5% were women. Most patients were asymptomatic (58.6%) and had monostotic disease (54.3%). Favorable responses were obtained in all patients who were treated with zoledronate (n = 36), in 10 out of 14 treated with pamidronate, in 9 out of 10 who received intravenous ibandronate and in 12 out of 13 who received oral bisphosphonates. The response rates were not significantly different when we compared monostotic vs. polyostotic disease. Among the biochemical parameters, mean values of bone specific and total alkaline phosphatase, and C-terminal crosslinked telopeptide of type I collagen decreased significantly after treatment with bisphosphonates. It seems that our results reflect the change in PDB epidemiology towards a more indolent disease. In the future, this would probably allow physicians to use lower doses of bisphosphonates than the ones historically recommended for these patients.

La epidemiología de la enfermedad de Paget ósea (EPO) ha cambiado en los últimos años. Son necesarios datos actualizados sobre su forma de presentación clínica, diagnóstico y tratamiento en nuestra región. Nuestro objetivo fue describir las características clínicas, evaluación diagnóstica y respuestas al tratamiento de un grupo de pacientes con EPO en un centro especializado en salud ósea de Buenos Aires, Argentina. Se evaluaron todos los pacientes que fueron atendidos en nuestra institución por enfermedades óseas entre junio de 2012 y diciembre de 2019. La frecuencia de EPO (180/10 714) fue de 1.68%. La mediana de edad fue de 67 (rango 39-97) años. El 59.5% eran mujeres. La mayoría se encontraba asintomático (58.6%) y tenían enfermedad monostótica (54.3%). Se objetivaron respuestas favorables en todos los que recibieron zoledronato (n = 36), en 10 de 14 pacientes que recibieron pamidronato, en 9 de 10 que utilizaron ibandronato endovenoso y en 12 de 13 con bifosfonatos orales. Los porcentajes de respuesta no variaron significativamente entre pacientes con formas monostóticas y poliostóticas. Entre los parámetros bioquímicos, los valores de fosfatasa alcalina total y ósea y de Β cross-laps disminuyeron significativamente luego del tratamiento con bifosfonatos. Nuestros resultados reflejarían un cambio en la epidemiología de la EPO hacia una forma de presentación más indolente. Esto permitiría probablemente el uso de dosis más bajas de bifosfonatos que las históricamente recomendadas para estos pacientes.

Hiperparatiroidismo primario normocalcémico

Presentamos las características clínicas, bioquímicas y densitométricas de 35 pacientes con hiperparatiroidismo primario (HPP) normocalcémico, que se caracteriza por un nivel elevado de hormona paratiroidea intacta (PTHi) con el calcio sérico y iónico persistentemente normales, una vez descartadas posibles causas de hiperparatiroidismo secundario. Del total, 30 fueron mujeres (90%) y 5 varones (10%). Se seleccionó un grupo control de 55 pacientes con hiperparatiroidismo primario hipercalcémico: 51 mujeres (93%) y 4 varones (7%). El promedio de edad al diagnóstico de HPP normocalcémico fue de 61.4 ± 11.7 años y del HPP hipercalcémico de 56.4 ± 11.3 años. Además de las diferencias esperables de la calcemia, el calcio iónico, el fósforo y la calciuria de 24 horas, no encontramos cambios significativos en el resto de las variables bioquímicas. Tampoco encontramos diferencias en los valores densitométricos, la presencia de osteopenia u osteoporosis y el número de fracturas entre ambos tipos de HPP. Sí hubo una diferencia significativa en la presencia de litiasis renal entre el HPP normocalcémico (11.4%) vs el HPP clásico (49.1%), p < 0.0005, en parte vinculada a la presencia de hipercalciuria en el HPP clásico. Dos de los 35 pacientes con HPP normocalcémico evolucionaron al HPP hipercalcémico durante un seguimiento de 4 años. Nuestros resultados apoyan la hipótesis que el HPP normocalcémico podría ser una forma temprana del HPP clásico, teniendo ambos similares repercusiones clínicas a nivel renal y óseo.

This report shows our conclusions on the clinical, biochemical and densitometry characteristics of 35 normocalcemic primary hyperparathyroidism (PHPT) patients. This condition is defined by a high level of intact parathyroid hormone (iPTHI) with persistently normal serum and ionized calcium in the absence of secondary hyperparathyroidism. Our selection consisted of 30 women (90%) and 5 men (10%). The control group of 55 hypercalcemic patients with primary hyperparathyroidism included 51 women (93%) and 4 men (7%). The average age at diagnosis of normocalcemic PHPT was 61.4 ± 11.7 years and 56.4 ± 11.3 years in hypercalcemic PHPT. Besides the expected differences in serum calcium, ionized calcium, phosphorus and 24 h urinary calcium, we found no significant changes in other biochemical variables, and no differences in densitometry evaluations such as the presence of osteopenia or osteoporosis and the number of fractures in the two types of PHPT. But there was a significant difference in the presence of renal lithiasis between normocalcemic PHPT (11.4%) and clasic PHPT (49.1%) p < 0.0005, to some extent associated to the presence of hypercalciuria in classic PHPT. Two of the 35 patients with normocalcemic PHPT became classic hypercalcemic PHPT over a 4 year follow-up period. Our findings support the hypothesis that the normocalcemic PHPT could be an early stage of the classic PHPT, both having similar clinical effects to metabolic renal and bone levels.

[Normocalcemic primary hyperparathyroidism]. / Hiperparatiroidismo primario normocalcémico.

This report shows our conclusions on the clinical, biochemical and densitometry characteristics of 35 normocalcemic primary hyperparathyroidism (PHPT) patients. This condition is defined by a high level of intact parathyroid hormone (iPTHI) with persistently normal serum and ionized calcium in the absence of secondary hyperparathyroidism. Our selection consisted of 30 women (90%) and 5 men (10%). The control group of 55 hypercalcemic patients with primary hyperparathyroidism included 51 women (93%) and 4 men (7%). The average age at diagnosis of normocalcemic PHPT was 61.4 ± 11.7 years and 56.4 ± 11.3 years in hypercalcemic PHPT. Besides the expected differences in serum calcium, ionized calcium, phosphorus and 24 h urinary calcium, we found no significant changes in other biochemical variables, and no differences in densitometry evaluations such as the presence of osteopenia or osteoporosis and the number of fractures in the two types of PHPT. But there was a significant difference in the presence of renal lithiasis between normocalcemic PHPT (11.4%) and clasic PHPT (49.1%) p < 0.0005, to some extent associated to the presence of hypercalciuria in classic PHPT. Two of the 35 patients with normocalcemic PHPT became classic hypercalcemic PHPT over a 4 year follow-up period. Our findings support the hypothesis that the normocalcemic PHPT could be an early stage of the classic PHPT, both having similar clinical effects to metabolic renal and bone levels.

Hiperparatiroidismo primario normocalcémico. / [Normocalcemic primary hyperparathyroidism].

This report shows our conclusions on the clinical, biochemical and densitometry characteristics of 35 normocalcemic primary hyperparathyroidism (PHPT) patients. This condition is defined by a high level of intact parathyroid hormone (iPTHI) with persistently normal serum and ionized calcium in the absence of secondary hyperparathyroidism. Our selection consisted of 30 women (90

) and 5 men (10

). The control group of 55 hypercalcemic patients with primary hyperparathyroidism included 51 women (93

) and 4 men (7

). The average age at diagnosis of normocalcemic PHPT was 61.4 ± 11.7 years and 56.4 ± 11.3 years in hypercalcemic PHPT. Besides the expected differences in serum calcium, ionized calcium, phosphorus and 24 h urinary calcium, we found no significant changes in other biochemical variables, and no differences in densitometry evaluations such as the presence of osteopenia or osteoporosis and the number of fractures in the two types of PHPT. But there was a significant difference in the presence of renal lithiasis between normocalcemic PHPT (11.4

) and clasic PHPT (49.1

) p < 0.0005, to some extent associated to the presence of hypercalciuria in classic PHPT. Two of the 35 patients with normocalcemic PHPT became classic hypercalcemic PHPT over a 4 year follow-up period. Our findings support the hypothesis that the normocalcemic PHPT could be an early stage of the classic PHPT, both having similar clinical effects to metabolic renal and bone levels.

[Severe osteoporosis treatment with teriparatide]. / Tratamiento de la osteoporosis grave con teriparatide.

The primary objective of this retrospective study was to evaluate the treatment of severe osteoporosis with teriparatide (PTH) and to compare our results with those published in the literature. We included 46 patients, 42 women and four men, mean age: 69.15 ± 9.43 years. Six patients were treatment naive and forty previously treated with bisphosphonates. Thirty-two patients had had 93 fractures of which 86 vertebral. Forty-six received PTH for 6 months, twenty-nine for 12 months and twenty completed the 18 months suggested. Bone mineral density (BMD) of the lumbar spine increased significantly at the first control performed at six months of treatment (p < 0.0001), and the femoral neck BMD reached a significant increase at the end of treatment (p = 0.002). Serum osteocalcin values significantly increased from the first month of treatment, followed by Β crosslaps (beta-CTx, serum test) and bone-specific alkaline phosphatase, returning all the markers of bone turnover to baseline levels at 18 months. Serum and urinary calcium did not change significantly at any time, but 8 (17.9%) patients developed mild hypercalcemia and 3 (6.5%) asymptomatic hypercalciuria. The treatment was well tolerated and there were no serious adverse events requiring discontinuation. In conclusion, PTH is a safe and useful alternative for the treatment of primary severe osteoporosis. Our results agree with those previously reported in the literature.

Tratamiento de la osteoporosis grave con teriparatide / Severe osteoporosis treatment with teriparatide

El objetivo de este trabajo retrospectivo fue evaluar el tratamiento de la osteoporosis grave con teriparatide (PTH) y comparar nuestros resultados con los publicados en la literatura médica. Se incluyeron cuarenta y seis pacientes, cuarenta y dos mujeres y cuatro varones, edad: 69.15 ± 9.43 años. Seis eran vírgenes de tratamiento y cuarenta tratados previamente con bisfosfonatos. Treinta y dos pacientes habían tenido 93 fracturas de las cuales 86 vertebrales. Cuarenta y seis recibieron PTH 6 meses, 29 pacientes durante 12 meses y 20 completaron los 18 meses sugeridos. La densidad mineral ósea (DMO) de columna lumbar aumentó significativamente desde el primer control a los 6 meses (p < 0.0001). La DMO de cuello de fémur alcanzó un incremento significativo al final del tratamiento (p = 0.002). La osteocalcina aumentó significativamente al mes, seguido por el ß crosslaps (beta-CTx, prueba en suero) al tercer mes y la fosfatasa alcalina ósea, regresando los marcadores de recambio óseo a niveles basales a los 18 meses. Las calcemias y las calciurias no se modificaron significativamente, pero 8 pacientes tuvieron hipercalcemias leves y tres hipercalciurias asintomáticas. El tratamiento fue bien tolerado y no se registraron efectos adversos graves que requirieran suspender el tratamiento. En conclusión, la PTH es una alternativa útil y segura para el tratamiento de la osteoporosis grave. Nuestros resultados concuerdan con los previamente publicados en la literatura médica.

The primary objective of this retrospective study was to evaluate the treatment of severe osteoporosis with teriparatide (PTH) and to compare our results with those published in the literature. We included 46 patients, 42 women and four men, mean age: 69.15 ± 9.43 years. Six patients were treatment naive and forty previously treated with bisphosphonates. Thirty-two patients had had 93 fractures of which 86 vertebral. Forty-six received PTH for 6 months, twenty-nine for 12 months and twenty completed the 18 months suggested. Bone mineral density (BMD) of the lumbar spine increased significantly at the first control performed at six months of treatment (p < 0.0001), and the femoral neck BMD reached a significant increase at the end of treatment (p = 0.002). Serum osteocalcin values significantly increased from the first month of treatment, followed by ß crosslaps (beta-CTx, serum test) and bone-specific alkaline phosphatase, returning all the markers of bone turnover to baseline levels at 18 months. Serum and urinary calcium did not change significantly at any time, but 8 (17.9%) patients developed mild hypercalcemia and 3 (6.5%) asymptomatic hypercalciuria. The treatment was well tolerated and there were no serious adverse events requiring discontinuation. In conclusion, PTH is a safe and useful alternative for the treatment of primary severe osteoporosis. Our results agree with those previously reported in the literature.

Tratamiento de la osteoporosis grave con teriparatide / Severe osteoporosis treatment with teriparatide

El objetivo de este trabajo retrospectivo fue evaluar el tratamiento de la osteoporosis grave con teriparatide (PTH) y comparar nuestros resultados con los publicados en la literatura médica. Se incluyeron cuarenta y seis pacientes, cuarenta y dos mujeres y cuatro varones, edad: 69.15 ± 9.43 años. Seis eran vírgenes de tratamiento y cuarenta tratados previamente con bisfosfonatos. Treinta y dos pacientes habían tenido 93 fracturas de las cuales 86 vertebrales. Cuarenta y seis recibieron PTH 6 meses, 29 pacientes durante 12 meses y 20 completaron los 18 meses sugeridos. La densidad mineral ósea (DMO) de columna lumbar aumentó significativamente desde el primer control a los 6 meses (p < 0.0001). La DMO de cuello de fémur alcanzó un incremento significativo al final del tratamiento (p = 0.002). La osteocalcina aumentó significativamente al mes, seguido por el ß crosslaps (beta-CTx, prueba en suero) al tercer mes y la fosfatasa alcalina ósea, regresando los marcadores de recambio óseo a niveles basales a los 18 meses. Las calcemias y las calciurias no se modificaron significativamente, pero 8 pacientes tuvieron hipercalcemias leves y tres hipercalciurias asintomáticas. El tratamiento fue bien tolerado y no se registraron efectos adversos graves que requirieran suspender el tratamiento. En conclusión, la PTH es una alternativa útil y segura para el tratamiento de la osteoporosis grave. Nuestros resultados concuerdan con los previamente publicados en la literatura médica.(AU)

The primary objective of this retrospective study was to evaluate the treatment of severe osteoporosis with teriparatide (PTH) and to compare our results with those published in the literature. We included 46 patients, 42 women and four men, mean age: 69.15 ± 9.43 years. Six patients were treatment naive and forty previously treated with bisphosphonates. Thirty-two patients had had 93 fractures of which 86 vertebral. Forty-six received PTH for 6 months, twenty-nine for 12 months and twenty completed the 18 months suggested. Bone mineral density (BMD) of the lumbar spine increased significantly at the first control performed at six months of treatment (p < 0.0001), and the femoral neck BMD reached a significant increase at the end of treatment (p = 0.002). Serum osteocalcin values significantly increased from the first month of treatment, followed by ß crosslaps (beta-CTx, serum test) and bone-specific alkaline phosphatase, returning all the markers of bone turnover to baseline levels at 18 months. Serum and urinary calcium did not change significantly at any time, but 8 (17.9%) patients developed mild hypercalcemia and 3 (6.5%) asymptomatic hypercalciuria. The treatment was well tolerated and there were no serious adverse events requiring discontinuation. In conclusion, PTH is a safe and useful alternative for the treatment of primary severe osteoporosis. Our results agree with those previously reported in the literature.(AU)

Tratamiento de la osteoporosis grave con teriparatide. / [Severe osteoporosis treatment with teriparatide].

The primary objective of this retrospective study was to evaluate the treatment of severe osteoporosis with teriparatide (PTH) and to compare our results with those published in the literature. We included 46 patients, 42 women and four men, mean age: 69.15 ± 9.43 years. Six patients were treatment naive and forty previously treated with bisphosphonates. Thirty-two patients had had 93 fractures of which 86 vertebral. Forty-six received PTH for 6 months, twenty-nine for 12 months and twenty completed the 18 months suggested. Bone mineral density (BMD) of the lumbar spine increased significantly at the first control performed at six months of treatment (p < 0.0001), and the femoral neck BMD reached a significant increase at the end of treatment (p = 0.002). Serum osteocalcin values significantly increased from the first month of treatment, followed by ÎÆ crosslaps (beta-CTx, serum test) and bone-specific alkaline phosphatase, returning all the markers of bone turnover to baseline levels at 18 months. Serum and urinary calcium did not change significantly at any time, but 8 (17.9

) patients developed mild hypercalcemia and 3 (6.5

) asymptomatic hypercalciuria. The treatment was well tolerated and there were no serious adverse events requiring discontinuation. In conclusion, PTH is a safe and useful alternative for the treatment of primary severe osteoporosis. Our results agree with those previously reported in the literature.

Optimum recombinant human thyrotropin dose in patients with differentiated thyroid carcinoma and end-stage renal disease.

OBJECTIVE: To evaluate serum thyrotropin (TSH) concentrations after conventional (0.9 mg) or half-dose (0.45 mg) administration of recombinant human TSH (rhTSH) injections intramuscularly in patients with end-stage renal disease and differentiated thyroid cancer. METHODS: In this case series, we administered 2 doses of 0.9-mg rhTSH or 2 doses of 0.45-mg rhTSH to 3 patients with renal failure and differentiated thyroid cancer who were receiving hemodialysis. Basal serum TSH concentrations were assessed while the patients were taking thyroid hormone therapy. Serum TSH was measured on days 2, 3, 5, 8, 10, 14, and 17 of the study. Thyroglobulin and thyroglobulin antibodies were also measured on days 5 and 7. Patients were asked to report any adverse effects. RESULTS: Patient 1, who received 2 injections of 0.9-mg rhTSH administered on days 1 and 3, had persistently elevated serum TSH levels for approximately 11 days. Peak serum TSH measured on day 5 was 644 mIU/L. Self-limited diarrhea was the only reported adverse effect. Patients 2 and 3 received 0.45 mg of rhTSH on 2 consecutive days (days 1 and 2), and both exhibited persistently elevated serum TSH levels for 12 days. The peak serum TSH values on day 3 were 402 mIU/L in Patient 2 and 386 mIU/L in Patient 3. No adverse events were observed in these 2 patients. Patient 2 received thyrotropin alfa for injection to confirm disease status. Patient 3 also received a radioiodine dose because of presumed persistent disease. CONCLUSION: High serum TSH levels achieved after conventional and half-dose administration of rhTSH suggest that a dose adjustment might be considered in patients with end-stage renal disease.