Prediction of bone mass changes after successful parathyroidectomy using biochemical markers of bone metabolism in primary hyperparathyroidism: is it clinically useful?

ABSTRACT Objective To measure type 1 serum amino-terminal propeptide procollagen (P1NP) and type 1 cross-linked C-terminal telopeptide collagen (CTX) before parathyroidectomy (PTX) in PHPT patients, correlating these measurements with bone mineral density (BMD) changes. Subjects and methods 31 primary hyperparathyroidism (HPTP) were followed from diagnosis up to 12-18 months after surgery. Serum levels of calcium, parathyroid hormone (PTH) vitamin D, CTX, P1NP, and BMD were measured before and 1 year after surgery. Results One year after PTX, the mean BMD increased by 8.6%, 5.5%, 5.5%, and 2.2% in the lumbar spine, femoral neck (FN), total hip (TH), and distal third of the nondominant radius (R33%), respectively. There was a significant correlation between BMD change 1 year after the PTX and CTX (L1-L4: r = 0.614, p < 0.0003; FN: r = 0.497, p < 0.0051; TH: r = 0.595, p < 0.0005; R33%: r = 0.364, p < 0.043) and P1NP (L1-L4: r = 0,687, p < 0,0001; FN: r = 0,533, p < 0,0024; TH: r = 0,642, p < 0,0001; R33%: r = 0,467, p < 0,0079) preoperative levels. The increase in 25(OH)D levels has no correlation with BMD increase (r = -0.135; p = 0.4816). On linear regression, a minimum preoperative CTX value of 0.331 ng/mL or P1NP of 37.9 ng/mL was associated with a minimum 4% increase in L1-L4 BMD. In TH, minimum preoperative values of 0.684 ng/mL for CTX and 76.0 ng/mL for P1NP were associated with a ≥ 4% increase in BMD. Conclusion PHPT patients presented a significant correlation between preoperative levels of turnover markers and BMD improvement 1 year after PTX.

Hiperparatiroidismo primario asintomático en mujeres / Asymptomatic primary hyperparathyroidism in women

El hiperparatiroidismo primario puede tener diferentes características. Una de ellas es la forma asintomática. Esta es una variante leve del hiperparatiroidismo primario hipercalcémico, que se caracteriza por una calcemia no mayor a 1 mg/dl sobre el límite superior del método, hormona paratiroidea intacta (PTHi) elevada, ausencia de litiasis renal, deterioro de la función renal y de osteoporosis, edad menor de 50 años, y calciuria menor a 400 mg/día. No es una entidad quirúrgica, pero en su evolución puede llegar a serlo. Se estudiaron 24 mujeres postmenopáusicas, todas mayores de 50 años, con diagnóstico de hiperparatiroidismo asintomático, se describieron las manifestaciones clínicas, los cambios densitométricos, los parámetros bioquímicos y del remodelado óseo y se compararon los resultados con las variantes clásica y normocalcémica de la enfermedad. Se establecieron los criterios diagnósticos y se observó que solo 2 (8.3%) de las pacientes, durante un seguimiento de 44 ± 12 meses tuvo necesidad de paratiroidectomía. En definitiva, el hiperparatiroidismo primario asintomático es una alteración benigna, de seguimiento clínico periódico que, en pocas ocasiones, durante el seguimiento puede requerir cirugía.

Primary hyperparathyroidism may have different characteristics. One is the asymptomatic form. This is a mild variant of hypercalcemic hyperparathyroidism, characterized by a calcemia not greater than 1 mg/dl above the upper limit of the method, a high intact parathyroid hormone (iPTH), absence of renal stones, renal function impairement, and osteoporosis, less than 50 years of age, and less than 400 mg/day calciuria. It is not a surgical entity, but its evolution may require it. Twenty-four postmenopausal women, all older than 50 years, with a diagnosis of asymptomatic hyperparathyroidism, were studied. Clinical manifestations, densitometric changes, biochemical parameters and bone remodeling were analyzed and the results were compared with the classic and normocalcemic variants of the disease. Diagnostic criteria were established and observed that only 2 (8.3%) of patients, during a follow up of 44 ± 12 months, had need for a parathyroidectomy. In conclusion, the asymptomatic primary hyperparathyroidism is a benign disorder, of periodic clinical follow-up, which rarely may require surgery.

Primary Hyperparathyroidism: The Influence of Bone Marrow Adipose Tissue on Bone Loss and of Osteocalcin on Insulin Resistance

OBJECTIVES: Bone marrow adipose tissue has been associated with low bone mineral density. However, no data exist regarding marrow adipose tissue in primary hyperparathyroidism, a disorder associated with bone loss in conditions of high bone turnover. The objective of the present study was to investigate the relationship between marrow adipose tissue, bone mass and parathyroid hormone. The influence of osteocalcin on the homeostasis model assessment of insulin resistance was also evaluated. METHODS: This was a cross-sectional study conducted at a university hospital, involving 18 patients with primary hyperparathyroidism (PHPT) and 21 controls (CG). Bone mass was assessed by dual-energy x-ray absorptiometry and marrow adipose tissue was assessed by 1H magnetic resonance spectroscopy. The biochemical evaluation included the determination of parathyroid hormone, osteocalcin, glucose and insulin levels. RESULTS: A negative association was found between the bone mass at the 1/3 radius and parathyroid hormone levels (r = -0.69; p<0.01). Marrow adipose tissue was not significantly increased in patients (CG = 32.8±11.2% vs PHPT = 38.6±12%). The serum levels of osteocalcin were higher in patients (CG = 8.6±3.6 ng/mL vs PHPT = 36.5±38.4 ng/mL; p<0.005), but no associations were observed between osteocalcin and insulin or between insulin and both marrow adipose tissue and bone mass. CONCLUSION: These results suggest that the increment of adipogenesis in the bone marrow microenvironment under conditions of high bone turnover due to primary hyperparathyroidism is limited. Despite the increased serum levels of osteocalcin due to primary hyperparathyroidism, these patients tend to have impaired insulin sensitivity.

Hiperparatiroidismo primario: Evolución postoperatoria a largo plazo / Primary hyperparathyrodism: Postoperative long-term evolution

Presentamos la evolución postoperatoria a largo plazo de 87 pacientes con hiperparatiroidismo primario. Del total, 78 mujeres y 9 varones, relación: 8.7:1. Edad media 55.3 ± 10.2 años. Antes de la cirugía el 44% presentó litiasis renal, el 70% osteopenia u osteoporosis y un 71.2% tuvo hipercalciuria. Se encontró disminución del filtrado glomerular en el 12.6%. Del total, 72 pacientes presentaron un adenoma único, dos un doble adenoma, dos hiperplasia, cuatro histología normal y en siete no se pudo disponer del resultado. El calcio sérico, el calcio iónico, el fósforo y la parathormona intacta se normalizaron en todos los pacientes postcirugía. La densitometría ósea aumentó un 6.9% en columna lumbar y un 3% en cuello de fémur. Los marcadores del remodelado óseo se normalizaron y persistieron normales a los 23 meses del seguimiento, coincidiendo con la parathormona intacta. Lo mismo sucedió con los valores de 25 OH D. Cuando se compararon pacientes con hipercalciuria inicial vs. aquellos con normocalciuria, no se encontraron diferencias en los valores basales y postcirugía en ambos grupos. En 11 pacientes con filtrado glomerular previo < 60 ml/min, encontramos una parathormona intacta más elevada que el resto y menor densidad mineral ósea. El filtrado glomerular no cambió en forma significativa luego de la cirugía. En conclusión, el hiperparatiroidismo primario operado por cirujanos especializados tiene una excelente evolución a largo plazo, con normalización de todos los parámetros del metabolismo fosfocálcico y del remodelado óseo y mejoría significativa en la densidad mineral ósea. Los efectos adversos son escasos y de resolución espontánea.

The long-term postoperative outcome of 87 patients with primary hyperparathyrodism is here presented. Of the total 78 were females and 9 males, ratio: 8.7:1. Mean age 55.3 ± 10.2 years. Before surgery, 44% had kidney stones, 70% had osteopenia or osteoporosis and 71.2% had hypercalciuria. Decrease renal glomerular filtration was found in 12.6%. Of the total, 72 patients had a single adenoma, two double adenoma, two hyperplasia, four had normal histology and seven could not dispose of the result. Serum calcium, ionized calcium, phosphorus and intact parathyroid hormone were normalized in all post surgery patients. Bone mineral density increased by 6.9% in lumbar spine and 3% in femoral neck. Markers of bone remodeling were normalized and persisted normal 23 months of follow-up, coinciding with the normal intact parathyroid hormone. Same thing happened with the values of 25 OH D. When patients whith initial hypercalciuria were compared with those with normocalciuria, no differences were found in the basal values and postsurgery in both groups. In 11 patients with previous renal glomerular filtration < 60 ml / min, we found a higher intact parathyroid hormone and lower bone mineral density than the rest. The glomerular filtration rate did not change significantly after surgery. In conclusion, the surgical primary hyperparathyroidism, operated by specialized surgeons has an excellent long-term outcome, with normalization of all parameters of phosphocalcic metabolism and bone remodeling and significant improvement in bone mineral density. Adverse effects were scarce and had spontaneous resolution.