Lack of Biochemical Progression or Continuation of Accelerated Bone Loss in Mild Asymptomatic Primary Hyperparathyroidism: Evidence for Biphasic Disease Course

Ds, Rao; Rj, Wilson; Kleerekoper, Michael; Am, Parfitt

doi:10.1210/jcem-67-6-1294

Cited by 217 publications

(114 citation statements)

References 19 publications

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“…pHPT is a relatively common endocrine disease with few overt manifestations, presenting most often as asymptomatic hypercalcemia [1]. Conservative management of patients with mild pHPT is not associated with progression of the disease, as reflected by long-term stable biochemical and bone densitometric indices [20,21]. A major challenge in the management of this disease is how to make the decision as to which patients should undergo PTX.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Changes in Bone Density and Biochemical Parameters after Parathyroidectomy in Primary Hyperparathyroidism.

et al. 2000

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Abstract.We examined the relationships between serum levels of intact parathyroid hormone (PTH) and alkaline phosphatase (ALP) versus bone mineral density (BMD) at the lumbar spine and radius in terms of their preoperative values and of their annual percentage and net changes after parathyroidectomy (PTX) in 44 Japanese patients (14 men and 30 women) with primary hyperparathyroidism (pHPT). Lumbar and radial BMD values were measured by dual energy X-ray absorptiometry and single photon absorptiometry and were used for evaluating the cancellous and cortical bone mass, respectively.Age-and sex-adjusted value (Z-score) of the radial BMD was significantly lower than that of the lumbar BMD before and after PTX (P<0.05).In preoperative patients, serum levels of both intact PTH and ALP were significantly and negatively correlated with Z-score of the radial BMD (P<0.05 and P<0.001, respectively), but not with that of the lumbar BMD. After PTX, serum levels of calcium, phosphorus, ALP, and PTH became normal, and both lumbar and radial BMD values markedly increased over 1 year, with percentage changes of 12.2± 1.4% and 11.6± 1.6%, respectively, which were larger than those in any other Caucasian study previously documented.Even in patients without osteopenia (Z-score of BMD >_ 0), lumbar and radial BMD values increased considerably after the operation (9.6± 1.9% and 6.7± 1.4%, respectively).Annual percentage and net changes in lumbar BMD were significantly and negatively correlated with those in ALP with high correlation coefficients, but those in radial BMD were correlated only with the annual net change in ALP but not with the percentage change. No significant correlations were observed between annual changes in either lumbar or radial BMD and those in intact PTH. Taken together, this study shows that PTX causes dramatic improvements in both the cancellous and cortical bone mass in Japanese pHPT patients regardless of the severity of their osteopenia, and suggests that the cancellous and cortical bones react differently to a preoperative endogenous PTH excess and a high bone turnover rate as well as to the postoperative normalization of a bone turnover rate in the patients. The cortical and cancellous bones also seem to react differently to the normalization of a high circulating level of PTH and of a high bone turnover rate which occurred after parathyroidectomy (PTX) in pHPT patients.Bone mineral density (BMD) has been reported to increase after PTX in Caucasian pHPT patients [11][12][13][14][15][16], and two studies have shown that the percentage increase in BMD of the lumbar spine after PTX was greater than that in BMD of the radius [16,17] . However, such clinical studies have yet to be performed in Japanese pHPT patients, and thus it remains unclear whether or not PTX has a similar beneficial effect on bone mass, or whether or not the recovery of bone loss after PTX is different between the cortical and cancellous bones in Japanese patients.In the present study, we assessed the cortical and cancellous bone mass in...

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Section: Discussionmentioning

confidence: 99%

Evaluation of Changes in Bone Density and Biochemical Parameters after Parathyroidectomy in Primary Hyperparathyroidism.

et al. 2000

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“…Over the past decade, a newer clinical description of PHPT has emerged, characterized by consistently normal total and ionized serum calcium concentrations with elevated PTH levels, in the absence of obvious causes for secondary hyperparathyroidism (41,(46)(47)(48). Individuals with this new phenotype, normocalcemic PHPT, are increasingly being discovered as many physicians are now requesting PTH levels in patients with, or suspected of, an underlying metabolic bone disease despite a normal serum calcium concentration (46-48).…”

Section: Normocalcemic Phptmentioning

confidence: 99%

“…Rao and cols. (41,42) monitored 80 asymptomatic patients for up to 11 years, during which time there was no worsening of biochemical or densitometric indices. Silverberg and cols.…”

Section: Skeletal Abnormalities In Asymptomatic Phptmentioning

confidence: 99%

Bone Disease in Primary Hyperparathyroidism

Parisien

Silverberg

Shane

et al. 1990

Endocrinology and Metabolism Clinics of North America

115

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Bone disease in severe primary hyperparathyroidism (PHPT) is described classically as osteitis fibrosa cystica (OFC). Bone pain, skeletal deformities and pathological fractures are features of OFC. Bone mineral density is usually extremely low in OFC, but it is reversible after surgical cure. The signs and symptoms of severe bone disease include bone pain, pathologic fractures, proximal muscle weakness with hyperreflexia. Bone involvement is typically characterized as saltand-pepper appearance in the skull, bone erosions and bone resorption of the phalanges, brown tumors and cysts. In the radiography, diffuse demineralization is observed, along with pathological fractures, particularly in the long bones of the extremities. In severe, symptomatic PHPT, marked elevation of the serum calcium and PTH concentrations are seen and renal involvement is manifested by nephrolithiasis and nephrocalcinosis. A new technology, recently approved for clinical use in the United States and Europe, is likely to become more widely available because it is an adaptation of the lumbar spine DXA image. Trabecular bone score (TBS) is a gray-level textural analysis that provides an indirect index of trabecular microarchitecture. Newer technologies, such as high-resolution peripheral quantitative computed tomography (HR-pQCT), have provided further understanding of the microstructural skeletal features in PHPT. KeywordsHyperparathyroidism; osteitis fibrosa cystica; nephrocalcinosis Copyright© ABE&M todos os direitos reservadosCorrespondence to: Francisco Bandeira, Disciplina de Endocrinologia, Faculdade de Ciências Médicas, Universidade de Pernambuco, Av. Rui Barbosa, 1435, 52050-450 -Recife, PE, Brasil, fbandeira@gmail.com. Disclosures: Dr. Bandeira is a consultant for Servier and Sanofi and receives research support from Amgen. Dr. Bilezikian is a consultant for Amgen, Eli Lilly, Radius, NPS Pharmaceuticals, Merck, and GSK, and receives research support from NPS Pharmaceuticals and Amgen. Drs. Silva, Cusano, Cassibba, Almeida and Machado: no conflicts of interest reported. In a series of 124 patients from Recife, about ten years ago, 25% of patients had severe skeletal involvement and OFC (1). Similar data were found in the city of São Paulo (5). NIH Public AccessMore recently, however, in a recent epidemiological study from the same institution with 4207 patients evaluated, only 6.1% had OFC (6).The aim of this work is to review current more relevant data on bone involvement in the various forms of primary hyperparathyroidism. Clinical manifestationsThe signs and symptoms of severe bone disease include bone pain, pathologic fractures, proximal muscle weakness with hyperreflexia. Although these patients usually present with non-specific symptoms such as weakness, depression and constipation, the dominant picture occurs due to severe bone abnormalities (1). Bone involvement is typically characterized as salt-and-pepper appearance in the skull (Figure 1), bone erosions and bone resorption of the phalanges (Figure 2), brown tumor...

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“…Surgery leads to normalization of biochemical abnormalities. Increased bone density has been reported in short-term (1-2 yr) randomized clinical trial data and long-term uncontrolled observational studies (up to 15 yr) (41)(42)(43)(62)(63)(64). The increase is seen earliest at the lumbar spine and hip but eventually also at the distal one-third radius.…”

Section: Treatment and Natural Historymentioning

confidence: 94%

“…However, strong evidence from both long-term observational studies and randomized trials of surgery vs observation in patients with mild PHPT demonstrate a salutary effect of surgical cure on bone density at the lumbar spine and hip, as well as the distal one-third radius (41)(42)(43)(62)(63)(64). These data are particularly striking in those with low bone density at time of diagnosis, with an increase of up to 20% in lumbar spine BMD reported in those with spine Z-scores < −1.5 (68).…”

mentioning

confidence: 99%