Effect of Bone Mineral Density and Parathyroidectomy on Fracture Risk in Primary Hyperparathyroidism

Background  Bone mineral density is one parameter used to decide whether patients with primary hyperparathyroidism (PHPT) should undergo parathyroidectomy. However, the influence of bone mineral density and parathyroidectomy on subsequent fracture risk is unclear. Methods  The authors conducted a retrospective cohort study of patients with PHPT based on administrative discharge abstract data. The dual energy x-ray absorptiometry (DEXA) scan T-scores at the femur were collected by chart review, and 10-year fracture-free survival (FFS) was the main outcome measured. Results  A total of 533 patients were identified, most of them ≥ 50 years old (89%) and female (87%). Seventeen percent of the patients were black. Mean initial calcium, parathormone, and creatinine levels were 11.1 mg/dl, 116 pg/ml, and 0.9 mg/dl, respectively. Parathyroidectomy was performed in 159 (30%) patients, and 374 (70%) were observed. The 10-year FFS after PHPT diagnosis was 94% in patients treated with parathyroidectomy and 81% in those observed (p = 0.006). Compared to observation, parathyroidectomy improved the 10-year FFS by 9.1% (p = 0.99), 12% (p = 0.92), and 12% (p = 0.02) in patients with normal bones (T-score ≥ −1.0), osteopenia (T-score ≤ −1.0, ≥ −2.5), and osteoporosis (T-score < −2.5), respectively. On multivariate analysis, parathyroidectomy was independently associated with decreased fracture risk (HR = 0.41; 95%CI 0.18, 0.93), whereas non-black race (HR = 2.94; 95%CI 1.04, 8.30) and T-score < −2.5 (HR = 2.29; 95%CI 1.08, 4.88) remained independently associated with increased fracture risk. Conclusions  Parathyroidectomy decreases the risk of fracture in patients with normal, osteopenic, and osteoporotic bones. The largest impact from parathyroidectomy is in patients with osteoporosis. The highest risk of fracture is in non-blacks and in patients with osteoporosis.     

Predictors of Bone Mineral Density Improvement in Patients Undergoing Parathyroidectomy for Primary Hyperparathyroidism

Introduction

Primary hyperparathyroidism (PHPT) results in increased bone turnover, resulting in bone mineral density (BMD) reduction and a predisposition towards fractures. Parathyroidectomy (PTX) is the only definitive cure.

Objective

The primary goals of this study were to investigate the impact of PTX on BMD in patients with PHPT and to identify factors associated with post-operative BMD improvement using a multivariate model.

Methods

Between 1999 and 2010, a total of 757 patients underwent PTX for treatment of PHPT; 123 patients had both a pre- and a post-operative dual-energy X-ray absorptiometry (DEXA) scan. A prospective database was queried to obtain information about patient demographics, medications, comorbidities, and pre- and post-operative laboratory values. A Cox regression model was used to stratify patients and to identify factors that independently predict BMD response following PTX in this patient population.

Results

Overall, mean percent change in BMD was +12.31 % at the spine, +8.9 % at the femoral neck (FN), and +8.5 % at the hip, with a mean follow-up of 2.3 ± 1.5 years. A total of 101 (82.1 %) patients had BMD improvement at their worst pre-operative site. In patients who improved, 69.9 % (n = 86) had >5 % increase. Factors associated with BMD improvement at the worst pre-operative site were as follows: male gender (hazard ratio [HR] 2.29; 95 % confidence interval [CI] 1.54–4.21); pre-operative BMD with T-score less than ?2.0 (HR 1.89; 95 % CI 1.11–2.39); age <55 years (HR 1.74; 95 % CI 1.14–2.25); BMD DEXA scan at >2.5 years post-operatively (HR 1.71; 95 % CI 1.09–2.17); history of previous fracture (HR 1.24; 95 % CI 1.05–1.92); and private insurance (HR 1.18; 95 % CI 1.06–2.1). The use of bisphosphonates, estrogens, vitamin D supplementation, or tobacco; obesity; history of previous PTX, serum calcium or parathyroid hormone levels were not independently associated with post-operative BMD improvement.

Conclusion

Osteoporosis is one of the established National Institutes of Health criteria for PTX in asymptomatic patients with PHPT, but BMD improvement is not consistently seen during the post-operative period. Gender, age, more severe pre-operative bone disease, and insurance status were all predictors for greater BMD improvement following PTX. Further studies with a rigorous post-operative BMD regimen are needed in order to validate these results.     

Skeletal Effects of Primary Hyperparathyroidism: Bone Mineral Density and Fracture Risk

Parathyroid hormone (PTH) is associated with anabolic and catabolic skeletal effects that vary according to the kinetics of serum levels and the type of bone. The anabolic effects are manifested in patients with a periodic rapid transient rise in serum PTH, as seen with daily subcutaneous injection of PTH(1–34) and PTH(1–84) in the treatment of osteoporosis. These patients have an increase in bone mineral density (BMD), particularly at skeletal sites with a high trabecular component, such as the lumbar spine, and a reduction in fracture risk. The catabolic effects are typified in patients with primary hyperparathyroidism (PHPT) who have chronic persistently elevated PTH levels. Patients with long-standing PHPT have a reduction in BMD, particularly at predominately cortical skeletal sites, such as the one-third radius, with relative preservation of BMD at the lumbar spine. Some but not all studies have reported an increase in fracture risk with PHPT. Because many patients with PHPT are postmenopausal women at risk for osteoporosis owing to estrogen deficiency, BMD and fracture risk may be a result of multiple factors with variable effects on bone remodeling. The skeletal effects of normocalcemic PHPT have not yet been fully characterized, but may not be the same as hypercalcemic PHPT.     

Bone Mineral Density in Menopausal Women with Primary Hyperparathyroidism before and after Parathyroidectomy

The relationship between osteoporosis and primary hyperparathyroidism (pHPT) has not been definitely established because both diseases occur predominantly in postmenopausal women, and because PTH has a paradoxical effect on bone. We have investigated the prevalence of reduced bone mineral density (BMD) in women with pHPT, its relationship with metabolic parameters, and its course after parathyroidectomy. A prospective observational study was carried out on perimenopausal and postmenopausal women consecutively diagnosed and operated on for pHPT. Demographic data were recorded, as well as, PTH, Ca, calciuria/24h, P, vitamin D, adenoma weight. The BMD was measured at three sites: femoral neck (FN), proximal femur (PF), and lumbar spine (LS). Fifty-two patients were included with a mean age of 61 ± 12 years. The prevalence of reduced BMD ( 1SD, T-score) was 80%–100% depending on site. Parathyroid hormone was higher in patients with osteoporosis (319 ± 181 pg/ml) than in those with osteopenia (230 ± 83 pg/ml) or normal BMD (148 ± 81 pg/ml; p < 0,04). Twenty-eight patients were investigated 1 year after parathyroidectomy. The BMD improved significantly at all sites, particularly in patients with osteoporosis. Age correlated inversely with BMD increases at the femoral sites (r= –0,47; p = 0,02) but not at the LS. 25-OHD₃ plasma levels correlated inversely with BMD increases at PF (r= –0,76; p < 0,0001). In pHPT, there is a high prevalence of BMD abnormalities. No metabolic variables had a definite influence on BMD values but a tendency was observed for lower BMD in severe pHPT. One year after parathyroidectomy, there were significant BMD increases that were more marked at femoral sites, in younger patients, in patients with preoperative osteoporosis, and in those with lower plasma levels of 25-OHD₃.This article was presented at the International Association of Endocrine Surgeons meeting, Uppsala, Sweden, June 14–17, 2004.     

Short- and Long-Term Changes in Bone Mineral Density of the Lumbar Spine After Parathyroidectomy in Patients with Primary Hyperparathyroidism

The aims of this study were (1) to analyze whether correlations exist between lumbar spine (LS) bone mineral density (BMD) and the main preoperative biochemical parameters in a large population of patients with primary hyperparathyroidism (HPT); and (2) to evaluate the LS-BMD changes after parathyroidectomy (PTx) at long-term follow-up. Sixty-two patients (median age 57 years, range 23–82 years) with confirmed primary HPT underwent LS osteodensitometry by dual-energy X-ray absorptiometry with BMD measurements at the L2–L4 region before surgery and at 1 year and 2 years after successful PTx. Three groups of patients were considered: Group A (men, n = 14, 22.6%), Group B (premenopausal women, n = 12, 19.3%), and Group C (postmenopausal women, n = 36, 58.1%). There were no linear correlations (P = NS) among the main biochemical parameters, the age of the patients, and their baseline LS-BMD values that were significantly (P < 0.01) lower in Group C patients. At 2-year follow-up the LS-BMD improved by 13.0%, 11.5%, and 11.7% in Groups A, B, and C, respectively (P = NS). In order to compare groups with the same linear relationship between age and LS-BMD, a subgroup of postmenopausal patients aged 60 years (Group C2) was considered. ANOVA showed that the improvement of the LS-BMD at l- and 2-year follow-up was higher (P = 0.002) in Group B than in Group C2 patients. The result was confirmed by using the Mann-Whitney U-test (P = 0.0078). Improvement of LS-BMD after successful PTx was significantly (P < 0.01) higher in premenopausal women, suggesting a possible role of estrogen hormone in complete bone remodeling. This study was presented at the XXVII European Symposium on Calcified Tissue, Tampere, Finland, 6–19 May, 2000     

Utility of Spine Bone Mineral Density in Fracture Prediction Within FRAX

Predicting individuals at risk for fracturing and modifying that risk are important in preventative health. Our aim was to quantify the impact of spine bone mineral density (BMD) on fracture risk prediction and determine the positive predictive value of fracture prediction using the lowest BMD value at the femoral neck, total hip, or lumbar spine. A retrospective cross-sectional analysis of 15,033 women was performed, assessing the contribution of age, body mass index, number of clinical risk factors, T-score, and osteoporosis category to the presence of fracture. In patients whose lumbar spine T-scores are 1 or 2 osteoporosis categories lower than femoral neck, there is an approximately 30% increased risk of fracture compared with the femoral neck alone. For patients younger than 60 yr, the odds ratio of having a fracture based on the presence of lumbar spine osteoporosis was greater than that based on femoral neck osteoporosis. Osteoporosis at the total hip correlated best with the presence of fracture. When using FRAX, we recommend that the 10-yr fracture prediction be adjusted when lumbar spine T-score is 1–2 osteoporosis categories lower than the femoral neck T-score or when lumbar spine T-score is ≥1 standard deviation less than femoral neck T-score.     

Calcimimetics and Bone Mineral Density in Renal Transplant Patients With Persistent Secondary Hyperparathyroidism

Background

The persistence of secondary hyperparathyroidism plays an important role in posttransplant bone loss. Calcimimetics are efficient to control metabolic alterations associated with this problem, but there are few publications that assess their effects on bone density.

Patients and Methods

This prospective study assessed the effects of a single daily dose of cinacalcet on calcemia, phosphatemia, parathyroid hormone (PTH), and bone densitometry (femur and spine) values of 27 renal transplant patients with stable kidney function, calcium > 10.5 mg/dL, and PTH > 65 pg/mL.

Results

A preliminary study after 6 months showed decreased calcemia (11.05 ± 0.5 to 10.18 ± 0.6 mg/dL; P < .0001), reduced levels of intact PTH (iPTH; 258 ± 104 to 209.61 ± 127 pg/mL; P < .05), and increased phosphatemia (2.38 ± 0.45 to 2.54 ± 0.3 mg/dL; P < .05). We also observed an increase in femoral neck bone mass with improved T score (−1.36 ± 1.19 to −1.05 ± 0.84 g/cm²; P < .05).

Conclusions

Cinacalcet was effective in the management of posttransplant persistent secondary hyperparathyroidism, resulting in decreased calcemia and iPTH, while also improving femoral neck bone loss. Longer-term studies with control groups are needed to determine the drug's influence on overall bone mineral density.     

Recovery of Bone Mineral Density in 126 Patients after Surgery for Primary Hyperparathyroidism

Primary hyperparathyroidism (pHPT) is associated with increased fracture risk and decreased bone mass. The recovery of bone mass after surgery varies; therefore tests that predict the increase in bone mass after parathyroidectomy would be desirable. Preoperatively and at 1 year after surgery bone mineral content (BMC) in the distal radius and bone mineral density (BMD) in the lumbar spine and hip, as well as biochemical variables, were measured in 126 pHPT patients (95 women, 31 men). The mean ± SD age of the patients was 63 ± 15 years. The mean ± SD serum calcium level was 2.78 ± 0.16 mmol/L. Altogether, 60% of the patients had a low oral calcium intake, and 18% had a 25-hydroxyvitamin D₃ deficiency. Preoperatively, postmenopausal women had lower Z-scores for BMD in the hip (p < 0.001) and lumbar spine (p < 0.05) than did premenopausal women. One year after surgery the bone density had increased in about 50% of the patients. The multiple logistic regression analysis showed that there was a weak association between the change in BMD in the hip, the serum 1,25-dihydroxyvitamin D₃ level (p < 0.05), and renal function (p < 0.05), respectively. We concluded that about 50% of patients have increased bone mass after pHPT surgery, but the increase in the bone density is difficult to predict for the individual patient. Because many pHPT patients have low oral calcium intake and a vitamin D deficiency, it would be of interest to evaluate the role of postoperative calcium/vitamin D supplements.     

Fracture Burden in Relation to Low Bone Mineral Density and FRAX Probability

Although the risk of fracture increases exponentially with declining bone mineral density, most fragility fractures have been shown to occur in individuals who do not meet the conventional densitometric definition for osteoporosis. The World Health Organization fracture risk assessment tool (FRAX^®) estimates individual 10-yr major osteoporotic and hip fracture probabilities. Intervention criteria based on risk assessment have been proposed by several groups, including the National Osteoporosis Foundation (NOF). We determined the relationship between 10-yr fracture probability and subsequent fracture burden in 36,730 women and 2873 men aged 50 yr and older. Using a major fracture probability cutoff of 20%, 29.4% of major osteoporotic fractures were identified in women and 4.9% in men. Based on a hip fracture probability cutoff of 3%, 54.1% of major osteoporotic fractures were detected in women and 53.4% in men. Using all NOF criteria, 65.9% of major osteoporotic fractures were detected in women and 69.3% in men. We conclude that men and women with FRAX probabilities below the high-risk NOF cutoffs have a high burden of major osteoporotic fractures. Strategies to enhance risk stratification in this group should be developed through international collaborations.     

Muscle Force and Bone Mineral Density after Parathyroidectomy and Subcutaneous Autotransplantation for Secondary Hyperparathyroidism

The object of this study was to determine the muscle force and bone mineral density (BMD) of patients with secondary hyperparathyroidism before and 3 months after operation. Thirty-nine patients with secondary hyperparathyroidism and regular dialysis were operated. Their ages were 47 ± 12 (mean ± SD) years and duration of dialysis was 70.5 ± 35.8 months. The clinical symptoms included bone pain in 23 patients (59%), skin itching in 21 (53.8%), general weakness in 13 (33.3%), conscious disturbance in 2, chest tightness in 1, and failure to thrive in 1. Total parathyroidectomy and autotransplantation of 60 mg of parathyroid gland into subcutaneous tissue was done routinely. BMD was measured in the lumbar spine (L2–L4) and left proximal femur, expressed as grams per square centimeter and as fracture risk. The extension force of the quadriceps muscle was measured at 60 degrees of right knee flexion, expressed as newtons (N) in a peak force and an average force. Three months after operation the BMD of the study group increased (in g/cm²) from 1.063 ± 0.181 to 1.148 ± 0.149 (p < 0.001) in L2–4 (n= 25), from 0.792 ± 0.14 to 0.875 ± 0.161 (p < 0.001), in femoral neck (n= 25), from 0.672 ± 0.171 to 0.754 ± 0.21 (p < 0.001) in Ward's triangle (n= 25), and from 0.69 ± 0.149 to 0.738 ± 0.143 (p < 0.001) in trochanter (n= 25). Fracture risk also was reduced significantly 3 months after operation at L2–4 (p= 0.003), femoral neck (p= 0.001), Ward's triangle (p= 0.003), and trochanter (p= 0.005). Muscle force (in newtons) increased from 264.8 ± 110.5 to 326 ± 110.9 (p= 0.023) in peak force (n= 18) and from 195.3 ± 90.4 to 258 ± 99 (p= 0.012) in average force (n= 18). The patients with general weakness had improved muscle force more prominently than those without general weakness. In addition to skin itching, bone pain, and soft tissue calcification, general weakness that causes disability is an indication for surgery in secondary hyperparathyroidism. After parathyroidectomy and autotransplantation, the muscle force tends to increase, especially in those with general weakness. An increment of BMD and reduction of fracture risk are also found after surgery.     

Prevalence of Primary Hyperparathyroidism and Impact on Bone Mineral Density in Elderly Men: MrOs Sweden

Background  

Age and sex are of importance in the development of primary hyperparathyroidism (PHPT), and the disease is most common in postmenopausal women. Skeletal complications are well known at an advanced stage of PHPT, although the impact on bone mineral density (BMD) is evident in patients with mild disease. This study examines the prevalence of PHPT in elderly men and its impact on BMD.     

Increase in Bone Mineral Density after Successful Parathyroidectomy for Tertiary Hyperparathyroidism after Renal Transplantation

BACKGROUND: Few studies have reported changes of bone mineral density (BMD) after parathyroidectomy in patients with persistent hyperparathyroidism after renal transplantation (3 HPT). PATIENTS AND METHODS: We retrospectively analyzed 14 patients who underwent successful parathyroidectomy for 3 HPT and who had available BMD data before and after parathyroidectomy. RESULTS: Median follow-up time was 26 months (IQR: 16.8-40.2). Serum calcium levels decreased significantly after parathyroidectomy (2.32 +/- 0.09 versus 2.66 +/- 0.16 mmol/l; p < 0.01), as did PTH levels (5.1 +/- 3.0 versus 27.8 +/- 23.7 pmol/l; p < 0.01). Nine patients (64%) had a steroid-free immunosuppression at follow-up. Mean increase in BMD was 9.5 +/- 8.0% for the spine and 9.5 +/- 7.9% for the hip (p < 0.01 for both sites). Patients with osteoporosis (T-score 相似文献   

Perspective on Fracture Risk and Phalangeal Bone Mineral Density

Current bone mineral density (BMD) represents the composite, cumulative effect of many past and present risk factors, including both genetic and lifestyle influences. Reduced BMD, increasing age, and the presence of pre-existing fractures independently increase the risk of osteoporotic fracture. BMD is the most clinically useful of these indicators. Assessment of phalangeal BMD by dual-energy X-ray absorptiometry (DXA) or radiographic absorptiometry (RA) has been shown to provide long-term value in predicting the risk of both hip and spine fracture. Data from phalangeal BMD measurements may be most valuable to the patient if they are used to compute the patient's remaining lifetime fracture probability (RLFP).     

The Impact of Bone Mineral Density on Bone Metabolism and the Fracture Healing Process in Elderly Chinese Patients With Osteoporotic Vertebral Compression Fractures

Background: The aim of this study was to investigate the effect of bone mineral density (BMD) on bone histomorphological parameters and bone turnover markers (BTMs) following osteoporotic vertebral compression fracture (OVCF) and to determine the correlation between BMD and the percentage of middle height compression during the healing process. Methods: A total of 206 patients with OVCFs were included in this study. Bone biopsy specimens were acquired during surgery. Blood samples were obtained to determine the serum concentrations of BTMs. The patients were divided into 2 groups according to BMD.Results: The concentrations of N-terminal propeptide of type I collagen (PINP) in the T-score ≤ ?2.5 group (50.92 ± 12.78 ng/ml) were significantly lower than those in the T-score > ?2.5 group (68.75 ± 28.66 ng/ml, p = 0.025) 3–6 mo after fracture. Moreover, the volume of necrotic bone in the T-score ≤ ?2.5 group (15.15 ± 5.44%) was higher than that (1.67 ± 0.79%, p < 0.001) in the T-score > ?2.5 group during the same period. BMD was statistically correlated with cancellous bone content (R_S = 0.761, p <0.001), PMHC (R_S = 0.85, p < 0.001), fibrous tissue volume (R_S = ?0.376, p < 0.001), and necrotic bone content (R_S = ?0.487, p < 0.001).Conclusions: The healing process of OVCFs in the setting of low bone mass frequently occurs in the presence of decreased bone formation abilities, severe vertebral body height loss and a large amount of necrotic bone.     

The Effect of Parathyroidectomy on Risk of Hip Fracture in Secondary Hyperparathyroidism

Background

Secondary hyperparathyroidism increases the risk for fractures. Despite improvement in medical therapy, surgical parathyroidectomy (PTX) often becomes necessary, but its effect on risk of fractures is not clear. Our aim was to study the effect of parathyroidectomy on the risk of hip fractures in patients on dialysis or with a functioning renal graft at time of parathyroidectomy.

Design

In a cohort of 20,056 patients on dialysis or with functioning renal allograft, we identified 590 patients who underwent parathyroidectomy between 1991 and 2009. Of these, 579 were matched with 1970 non-PTX patients on age, sex, cause of renal disease and functioning renal allograft or not at the time of PTX or at the corresponding time for non-PTX patients (t). We calculated the risk for hip fracture after PTX using crude and adjusted Cox proportional hazards regressions, adjusting for time in renal replacement therapy before t, time with functioning renal allograft before and after t, comorbidity at t and a hip fracture before t.

Results

The adjusted hazard ratio (95% confidence interval) for hip fracture was 0.40 (0.18–0.88) for PTX patients, compared to non-PTX patients. When analyses were performed separately for sex, only women had a lower risk of hip fracture after PTX compared to non-PTX patients. The risk of hip fracture after PTX was similar in patients with or without functioning renal allograft at time for PTX.

Conclusion

Parathyroidectomy is associated with a lower risk of hip fracture in female patients with secondary hyperparathyroidism.

     

Quantitative Ultrasound and Bone Mineral Density in Patients with Primary Hyperparathyroidism Before and after Surgical Treatment

The aim of this study was to assess the pattern of ultrasound (QUS) parameters and bone mineral density at different skeletal sites in patients with primary hyperparathyroidism (PHPT) before and after surgical treatment. In 22 patients (age range 28–74 years) with PHPT we measured speed of sound (SOS), attenuation (BUA) and Stiffness at the calcaneus, amplitude-dependent speed of sound (AD-SoS) at proximal phalanges, and bone mineral density at lumbar spine (BMD-LS) and at the mid-radius (BMD-MR) and ultradistal radius (BMD-UDR) before, 1 and 2 years after surgical operation. Twenty-two age- and sex-matched healthy subjects provided control data. Before surgery, all parameters apart from SOS were significantly lower in PHPT patients than in controls. At the end of the study period, BMD-LS increased by 7.0%, BMD-UDR by 7.4% and BMD-MR by 11.0%. The changes in ultrasound parameters after surgery were lower (0.44% for SOS, 2.2% for BUA, 3.3% for Stiffness and 2.6% for AD-SoS); however, the increase was statistically significant (p<0.05 and p<0.01, respectively) only for Stiffness and AD-SoS. Our results indicate that parathyroidectomy increases both axial and appendicular BMD and influences QUS parameters differently at the calcaneus and at the phalanges. The combined use of BMD and QUS could improve the assessment of skeletal status in patients with PHPT before and after surgery. Received: 22 January 1999 / Accepted: 25 August 1999