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Keywords:

  • bone;
  • bone mineral density;
  • mild primary hyperparathyroidism;
  • osteoporosis;
  • surgery

Abstract.

  1. Top of page
  2. Abstract.
  3. Background
  4. Method
  5. Results
  6. Discussion
  7. Conflict of interest statement
  8. Acknowledgements
  9. References

Objectives.  Patients with mild primary hyperparathyroidism (pHPT) often appear asymptomatic, and have previously been regarded as not requiring treatment. However, increased cardiovascular morbidity and dyslipidaemia have also been recognized in mild pHPT, which also seem to be normalized after parathyroidectomy. The present study explores whether postmenopausal women with mild pHPT have decreased bone mineral density (BMD) compared with age-matched healthy controls, and the effects on BMD of parathyroidectomy.

Design, Subjects and Intervention.  A population-based health screening of 5202 postmenopausal women identified 87 overtly asymptomatic patients with mild pHPT as well as age-matched healthy controls. A 5-year follow-up included 49 cases who had undergone parathyroidectomy. BMD was measured with DXA at the femoral neck, the lumbar spine and the total body.

Results.  At study entry, BMD was 5–6% lower in the lumbar spine (L2-L4) and femoral neck in cases compared with matched controls. After the 5-year follow-up, BMD increased in L2-L4 by 2.9% (P = 0.002) in the parathyroidectomized cases and remained stable in the femoral neck. However, femoral neck BMD increased 4.1% (P = 0.013) for cases <67 years old (50% of the cohort).

Conclusion.  In accordance with recent NIH guidelines for pHPT treatment, the level of BMD per se in the investigated group of patients justifies parathyroidectomy in almost half of the cases with mild pHPT. Surgery could be expected to increase BMD in L2-L4 to the level of the controls, to increase femoral neck BMD in patients <67 years of age and to preserve femoral neck BMD in the elderly population.


Background

  1. Top of page
  2. Abstract.
  3. Background
  4. Method
  5. Results
  6. Discussion
  7. Conflict of interest statement
  8. Acknowledgements
  9. References

Primary hyperparathyroidism (pHPT) is a common endocrine disease that affects 1% of the adult population and up to 3% of postmenopausal Swedish women [1, 2]. Whilst the prevalence of symptomatic pHPT may be decreasing in the Western World, the widespread use of, and easy access to, automated multi-channel serum analysers lead to increased detection of mild and asymptomatic pHPT. Mild and asymptomatic pHPT is a therapeutic challenge due to the scarcity of information on the potential risks and benefits of different treatments [3]. Another controversy involves ‘nontraditional’ manifestations, such as hypertension, serum lipoprotein abnormalities, decreased glucose tolerance, and increased morbidity and mortality from cardiovascular diseases [4–7]. Several reports suggest that these noncharacteristic phenomena of pHPT are also present in asymptomatic as well as in normocalcemic diseases [5, 7, 8]. Whilst low bone mineral density (BMD) is a traditional manifestation of pHPT [9, 10], studies of the characteristic presentation in mild pHPT are contradictory [11, 12]. In addition, population-based analyses of BMD in mild and asymptomatic pHPT have not been presented.

The present study is a systematic search for mild, asymptomatic pHPT in association with population-based mammography screening of postmenopausal women [1]. The aim of the study was to investigate BMD levels in patients with mild and asymptomatic pHPT, compared with age-matched controls, and to evaluate the effects of parathyroidectomy on BMD after a 5-year follow-up.

Method

  1. Top of page
  2. Abstract.
  3. Background
  4. Method
  5. Results
  6. Discussion
  7. Conflict of interest statement
  8. Acknowledgements
  9. References

At a population-based health screening of 5202 postmenopausal women, 87 cases with asymptomatic mild pHPT were identified (Fig. 1). The women were initially recruited if they had serum calcium below 3.0 mmol L−1, serum creatinine <160 μmol L−1 (normal range 64–106 μmol L−1), and no family history of hypercalcemia as well as normal or high urine calcium excretion [1]. To identify cases with mild and asymptomatic pHPT amongst the individuals initially identified, a second recruitment level was installed. Thus, individuals with hypercalcemia (>2.60 mmol L−1) combined with serum parathyroid hormone (PTH) ≥ 25 ng L−1 (normal range 12–55 ng L−1), or serum calcium 2.50–2.60 mmol L−1 and PTH ≥ 35 ng L−1, or serum calcium <2.50 mmol L−1 and PTH >55 ng L−1 were identified [1]. The serum calcium and PTH levels that were used to identify mild pHPT, were based on previous pathophysiological information on parathyroid gland function. Levels of inclusion criteria were chosen to include all cases with possible pHPT, also cases with serum calcium and PTH levels within the normal reference range. Later parathyroidectomy also substantiated the presence of pathological parathyroid glands in all selected individuals [13]. The identified cases had mean serum calcium of 2.57 (±0.12) mmol L−1 (range 2.36–2.92 mmol L−1) and s-PTH of 53.6 (±22) ng L−1 (range 25–150 ng L−1). Thus, identified individuals with overt pHPT (serum calcium >3.0 mmol L−1) or with symptoms related to pHPT, were excluded from the study. The cases were divided into two groups, observed and parathyroidectomized patients respectively. A control individual was selected from the screened population by matching for age as well as for the quarter of the year in which the laboratory examination was performed. The controls had to have serum calcium <2.55 mmol L−1 without falling into our criteria of mild pHPT and serum creatinine <160 μmol L−1 [1]. Serum calcium levels upon entering the study did not differ between those later operated on or unoperated cases [13].

image

Figure 1. Flow chart of patients and controls in the follow-up study.

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Cases and controls had similar body mass index (BMI), smoking and daily exercise habits, and were well matched with respect to age (Table 1). Menopausal age averaged 5.0 (±4.05) years within the case–control pairs, and did not differ significantly between cases and controls [1]. All subjects gave informed consent to participate in the study, which was approved by the local Ethics Committee.

Table 1.  Biochemical values, body composition and bone mineral variables of cases (n = 87), controls (n = 87) and treatment subgroups (at follow-up parathyroidectomized cases n = 49 and conservatively observed cases n = 20) at study inclusion.
VariableCasesControlsPaSub groupPb
Operated casesObserved cases
  1. Values are presented as mean ± SD. PTH, parathyroid hormone; BMC, bone mineral content; BMD, bone mineral density; NS, not significant. aPaired t-test. bUnpaired t-test. cCalculated as body weight/(height)2. *P < 0.05; **P < 0.01; ***P < 0.001.

Age (years)66.7 ± 5.866.7 ± 5.8NS65.6 ± 5.866.5 ± 5.3NS
Intact s-PTH (ng L−1)53.6 ± 2229.5 ± 9.7***56.6 ± 2347.5 ± 19NS
Total s-calcium (mmol L−1)2.57 ± 0.122.36 ± 0.07***2.58 ± 0.132.54 ± 0.08*
Ionized p-calcium (mmol L−1)1.28 ± 0.061.17 ± 0.03***1.29 ± 0.061.25 ± 0.03NS
s-Alkaline phosphatases (μkat L−1)3.36 ± 1.13.55 ± 4.8*3.46 ± 1.53.02 ± 0.79NS
s-Creatinine (μmol L−1)83.7 ± 1384.5 ± 13NS83.0 ± 1487.8 ± 14NS
Weight (kg)70.0 ± 1368.5 ± 11NS69.8 ± 1273.4 ± 12NS
Height (m)1.62 ± 0.051.62 ± 0.06NS1.61 ± 0.061.61 ± 0.05NS
BMI (kg m−2)c26.8 ± 5.026.1 ± 4.3NS26.9 ± 4.528.4 ± 5.0NS
L2-L4 BMD (g cm−2)0.963 ± 0.171.02 ± 0.18*0.966 ± 0.180.996 ± 0.15NS
 T-score−1.97 ± 1.4−1.46 ± 1.5*−1.94 ± 1.5−1.70 ± 1.2NS
 Z-score−0.322 ± 1.20.190 ± 1.4*−0.342 ± 1.3−0.162 ± 10.2NS
Neck BMD (g cm−2)0.774 ± 0.120.815 ± 0.11*0.775 ± 0.110.822 ± 0.12NS
 T-score−1.72 ± 0.98−1.38 ± 0.90*−1.71 ± 0.91−1.32 ± 1.1NS
 Z-score−0.317 ± 0.840.028 ± 0.84*−0.348 ± 0.80.001 ± 1.0NS
Total body BMD (g cm−2)1.00 ± 0.11.06 ± 0.09***1.01 ± 0.101.03 ± 0.09NS
 T-score−1.49 ± 1.2−0.871 ± 1.2***−1.48 ± 1.2−1.23 ± 1.2NS
 Z-score−0.507 ± 0.900.206 ± 1.0***−0.504 ± 0.9−0.372 ± 1.0NS
Total body BMC (g)2130 ± 3842280 ± 345*2133 ± 3912217 ± 328NS

Parathyroidectomies were performed as standard bilateral neck exploration under general anaesthesia. Controls were excluded from further follow-up when the matching cases left the study.

Biochemistry and bone mineral density

Biochemical values were determined after an overnight fast. Total serum calcium (normal range 2.20–2.60 mmol L−1) was measured using ortho-cresolphthalein dye binding and corrected for serum albumin by using the normal mean of females above 50 years of age [14]. Ionized plasma calcium (normal range 1.10–1.30 mmol L−1) was determined with an ion sensitive electrode (Kone Instruments, Espoo, Finland), and serum creatinine (normal range 64–106 μmol L−1) according to Jaffe. Intact serum PTH (normal range 12–55 ng L−1) was measured with a radioimmunometric assay (Nichol's Institute, San Juan Capistrano, CA, USA). BMI was calculated as the weight (kg) divided by the square of the body length (m2).

Dual energy X-ray absorptiometry, DXA (DPX-L; Lunar Co., Madison, WI, USA) was used to measure BMC (bone mineral content) for the total body and BMD in lumbar spine (L2–L4), left proximal femur and for the total body. The T-score was calculated as the difference in standard deviation (SD) from a young adult US white female reference population (provided by the manufacturer). Longitudinal precision of measurements on a spine phantom estimated a coefficient of variation of <1% during the study period. T-score below −1 SD is regarded as osteopenia and below −2.5 SD as osteoporosis [15]. Z-score was calculated as the difference in SD from an age- and weight-matched US white female reference population (provided by the manufacturer). DXA measurements were blinded to the investigators. The data were stored digitally and all measurements were re-evaluated by one of the authors (HM) after conclusion of the 5-year follow-up, blinded for participant status and therapeutic regime.

Standing height was measured at baseline and at 1 and 5 years in association with DXA measurements, using a Harpender Stadiometer (Holtain Ltd, Crymych, UK). Calibration of the height instrument was made daily.

Statistics

Paired and unpaired two-tailed t-tests and Spearman's rank correlation analyses were used for statistical analyses. P < 0.05 was considered significant. Values are presented as mean and SD.

Results

  1. Top of page
  2. Abstract.
  3. Background
  4. Method
  5. Results
  6. Discussion
  7. Conflict of interest statement
  8. Acknowledgements
  9. References

Cases and controls

Our intention to randomize the patients to parathyroidectomy or surveillance failed due to cases’ refusal to undergo surgery or elderly cases’ operative risks. Therefore, all cases without contraindications for parathyroidectomy were recommended surgery 1 year after entering the study. The cases in the surveillance group are presented in baseline characteristics for comparison only, and are excluded from further analyses due to possible selection bias (Table 1).

The final follow-up examination was performed approximately 5 years after inclusion (67.9 (±4.7) months), and included 69 cases (62 controls). Ten cases (five controls) had migrated or left the study for other reasons and eight cases (three controls) had died. Parathyroidectomy was performed in 49 cases 46.0 (±12.2) months before the 5-year investigation. Eleven of these had also received hormone replacement therapy (HRT oral oestradiol, 2 mg and norethisterone, 1 mg daily) for an average of 31.4 (±20.3) months. During the 5-year period, 20 controls received HRT for variable periods of time and one control developed pHPT. One case and two controls had vitamin D or calcium supplementation. No subjects were treated with bisphosphonates. Stratifying for HRT treatment amongst the cases and the controls did not demonstrate any confounding effect on calcium homeostasis or BMD, which is why these individuals are presented together in the present series.

Inclusion

At inclusion, the 87 cases had higher serum calcium and PTH values than the controls, as well as lower BMD and T-scores than their controls in all evaluated areas with −5.3% to −5.9% differences (P = 0.0006–0.03). Z-scores followed a pattern similar to T-scores. Cases in the parathyroidectomized and surveilled subgroups had the same biochemical and BMD values (Table 1). T-scores in lumbar spine and femoral neck for 86% of the cases were lower than −1.0 SD. The proportion of cases and controls with a T-score lower than −2.5 SD in the femoral neck were higher in cases than in controls (Table 2).

Table 2.  Cases and controls with T-score lower than −2.5 and −1.0 SD, respectively, at inclusion
 CaseControlPa
  1. Values are presented as a percentage of total number of cases and controls (n = 87). NS, not significant. aChi-squared test. *P < 0.05.

T-score<−2.5 SD<−2.5 SD 
Lumbar spine42%28%NS
Femoral neck22%13%*
Lumbar spine or femoral neck45%35%NS
T-score<−1.0 SD<−1.0 SD 
Lumbar spine or femoral neck86%80%NS

Total serum calcium and ionized calcium correlated negatively with BMD in both spine and total body (r = −0.260 to −0.302, P = 0.005–0.02). This correlation persisted when weight was considered as a possible confounder of the BMD value (P = 0.02–0.03). Amongst these cases, calcium explained 7–9% of the BMD values according to the regression coefficient. PTH had no discernible association with BMD at any site. Alkaline phosphatases correlated negatively with total body BMD (r = −0.234, P = 0.03). None of these correlations were noted in the controls.

Cases with total serum calcium above the upper reference limit (>2.60 mmol L−1; n = 21) had lower BMD and T-score in lumbar spine and total body than cases with serum calcium in the normal range (n = 58; P = 0.0004–0.01). A corresponding difference in BMD for serum PTH above and below the upper reference limit (>55 ng L−1) could not be identified.

There were no correlations between age and BMD in any of the investigated areas.

Follow-up

Before the 5-year follow-up, an interim analysis was performed 1 year after inclusion in the study. At this time, operated cases already demonstrated a gain in BMD, but at a lower magnitude than at 5 years. At the 5-year follow-up, parathyroidectomized cases (n = 49) were normalized in total and ionized calcium as well as PTH values to the level of the controls, indicating successful surgery (Table 3). Follow-up in operated cases occurred on average 46.0 (±12.2) months after parathyroidectomy. In these individuals, BMD of the lumbar spine had increased by 2.9% (P = 0.002) when compared with at study entry. Femoral neck BMD remained at the same level at follow-up, whilst total body BMD decreased by 1.8% (P = 0.02). Parathyroidectomized cases decreased by 0.2 cm in height over time (NS). At follow-up, there were no longer any differences in BMD or T-scores between parathyroidectomized cases and their matched controls (1Tables 1 and 3). The change in BMD in parathyroidectomized cases was positive and differed significantly from the negative change seen in the controls, both in L2-L4 (P = 0.02) and femoral neck (P = 0.04, Fig. 2).

Table 3.  Biochemical values, body composition and bone mineral variables of parathyroidectomized cases (n = 49) and control individuals (n = 68) at the time of inclusion and at follow-up
VariableParathyroidectomyChange in patients versus change in controls (Pb)Controls
InclusionFollow-up% changeaPaInclusionFollow-up% changeaPa
  1. Values are presented as mean ± SD. NS, not significant. aComparison between inclusion and follow-up, paired t-test. bDifference between change in cases and change in controls over 5 years. + or − sign indicates increased or decreased values compared with matched controls (cases regarded as baseline values), paired t-test. cCalculated as body weight/(height)2. *P < 0.05; **P < 0.01; ***P < 0.001.

Age (years)65.7 ± 5.871.0 ± 5.766.0 ± 5.771.7 ± 5.8
Intact s-PTH (ng L−1)56.7 ± 2335.4 ± 16−37.6***−25.3***28.8 ± 9.232.8 ± 1412.2**
Total s-calcium (mmol L−1)2.58 ± 0.132.34 ± 0.10−9.3***−0.25***2.36 ± 0.082.37 ± 0.090.4NS
Ionized p-calcium (mmol L−1)1.29 ± 0.061.14 ± 0.05−11.6***−0.14***1.17 ± 0.031.16 ± 0.04−0.9**
Weight (kg)70.9 ± 1371.5 ± 120.8*NS69.1 ± 1169.8 ± 111.0*
Height (m)1.61 ± 0.061.61 ± 0.060.0NSNS1.63 ± 0.061.62 ± 0.06−0.6***
BMI (kg m−2)c27.3 ± 4.827.8 ± 4.61.8**NS26.3 ± 4.626.6 ± 4.21.1***
L2-L4 BMD (g cm−2)0.967 ± 0.181.00 ± 0.182.9**+0.053*1.03 ± 0.181.01 ± 0.17−1.7NS
Neck BMD (g cm−2)0.774 ± 0.110.776 ± 0.120.8NS+0.023*0.827 ± 0.110.806 ± 0.11−2.5*
Total body BMD (g cm−2)1.01 ± 0.101.00 ± 0.09−1.8*+0.03*1.06 ± 0.091.02 ± 0.08−3.6***
Total body BMC (g)2130 ± 3942160 ± 3841.4NSNS2290 ± 3162220 ± 277−3.1***
image

Figure 2. Change in bone mineral density during the study period at lumbar spine (L2-L4) and femoral neck of parathyroidectomized cases (PTx) and controls. *Difference in change between inclusion and follow-up of parathyroidectomized cases compared with controls (paired t-test, P < 0.05).

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Age correlated with change in BMD over time in the femoral neck (r = −0.326, P = 0.025), but not in L2-L4 or total body for operated cases. Cases <67 years of age had a mean BMD (g cm−2) at study inclusion of 0.971 (±0.19), 0.781 (±0.10) and 1.021 (±0.1) in L2-L4, femoral neck and total body, respectively, whilst corresponding values for cases ≥67 years of age were 0.963 (±0.17), 0.766 (±0.12) and 0.994 (±0.1). Increase in BMD was more pronounced in parathyroidectomized cases below 67 years of age at study entry (mean and median age parathyroidectomized cases 66 years, n = 48; 25 cases <67 years, 23 cases ≥67 years), comprising 4.1% (P = 0.007) in L2-L4 and 2.5% (P = 0.013) in femoral neck, compared with baseline, reaching the level of the controls. The corresponding difference was not seen in total body BMD. Cases ≥67 years of age did not change in L2-L4 or in the femoral neck postoperatively, but increased in total body by 2.0% (P = 0.013). There were no differences in BMD change in controls stratified for age.

The controls (n = 62) demonstrated slightly lower ionized calcium and higher PTH values at follow-up than at inclusion. The controls had decreased in height (0.6 cm), and in BMD in L2-L4, neck and total body by 0.6–3.6% (P < 0.0001–0.05, Table 3).

Discussion

  1. Top of page
  2. Abstract.
  3. Background
  4. Method
  5. Results
  6. Discussion
  7. Conflict of interest statement
  8. Acknowledgements
  9. References

This study demonstrates significant bone loss in a group of postmenopausal women with truly mild and asymptomatic pHPT. All examined cases were considered asymptomatic at study entry and those with classical symptoms of pHPT or serum calcium above 3.00 mmol L−1 were excluded from further investigation. Moreover, the cases were recruited from a screened population in a longitudinal and prospective setting, including assignment of age-matched controls.

According to the recommendations of the 1990 Consensus Conference [16], all but 11 of the 87 (88%) women would have met the criteria for conservative follow-up. However, recommendations from a more recent workshop offering guidelines for treatment of pHPT would lead to parathyroidectomy in 37 patients (43%) due to the BMD data per se [4, 15]. In fact, as many as 45% of the cases had a T-score of −2.5 SD or lower at lumbar spine or femoral neck, compared with 35% of the matched controls. In this respect, it should be noted that neither of the documents presenting guidelines considers the diagnosis of pHPT unless serum calcium is elevated above the normal range.

Another principal finding is that the recorded osteopenia was partially reversible during a 5-year period and that parathyroidectomy can be expected to increase BMD of lumbar spine to the level of age-matched controls in all age groups, and in patients <67 years of age also in the femoral neck. The decrease in BMD over time seen in the femoral neck in patients ≥67 years of age with mild pHPT may be diminished, although not normalized towards their controls, by parathyroidectomy. Whilst the parathyroidectomized cases decreased only by 0.2 cm in height, the controls decreased by 0.6 cm. This finding indirectly supports the positive effects of parathyroidectomy on lumbar spine BMD.

More explicitly, our results substantiate the causal coupling between bone derangements and mild parathyroid disorder. The difference between cases and controls should not be considered as fortuitous. The results also confirm that PTH hypersecretion affects the skeleton adversely despite the fact that serum calcium is within the normal reference range or only slightly raised together with inappropriately high but normal serum PTH values.

A unique feature of the study is the population-based approach and recruitment of the patients. This allows characterization of the disease in a uniquely representative sample of females with minimized risks of confounding related to both the patients and the treating doctors.

Previous cross-sectional studies of BMD progression after menopause indicate a sharp postmenopausal decrease, followed by a more moderate slope vector [3]. Parts of this slope may be seen in our control individuals, but the generally lower values seen in the pHPT individuals should also be noted. Thus, as in the control individuals in this investigation, recent longitudinal studies of BMD loss after menopause demonstrate a decrease in the magnitude of 0–0.9% per year [17]. Lack of relationship between age and BMD in pHPT in the cases might be due to the complex disturbances of bone structure in pHPT. A decreased cortical BMD with increased cortical outer, but decreased cortical inner rim, combined with effects on cancellous bone due to PTH excess, and BMD decrease due to age will make these data difficult to assess [18].

The BMD gain after surgery was limited to the lumbar spine in the total cohort, whereas in other studies recovery was also noted in the femoral neck [3, 19–21]. Our total cohort could not verify other authors’ results from the femoral neck, but if the material was dichotomized by age, an increase of BMD in the femoral neck reaching the levels of the controls could be verified. This discrepancy may be due to the mild disease in our cohort with a mean calcium level of 2.57 mmol L−1, in contrast to other studies of overt pHPT and serum calcium above 2.70 mmol L−1. Furthermore, the mean age of the included cases was higher in our material than in other reports, especially at the 5-year follow-up.

Bone mineral density was measured at sites reflecting cortical bone status, i.e. total body, and sites believed to consist of mainly equal portions of cancellous and cortical bone, i.e. lumbar spine and femoral neck. For technical reasons we could not investigate the forearm BMD at the start of the study. The forearm is dominated by cortical bone and is usually the area where the most advanced bone loss can be found in clinically detected pHPT [22]. This suggests that we may have underestimated the proportion of females with osteoporosis due to mild pHPT and their need for parathyroidectomy according to the current treatment strategy [4].

Generally, a decrease in BMD in pHPT is associated with an increased incidence of fractures [23], especially of the vertebrae and distal forearm, but not in the femoral neck [24]. Parathyroidectomy has previously been shown to reduce this risk compared with surveillance [25, 26]. It has not yet been proved whether there is also an increased fracture risk in mild pHPT. The present material includes too few cases to clarify this issue.

The same method and equipment for bone density measurements were utilized throughout the study to decrease the risk of introducing a confounding effect by, for example, utilizing both single and double energy X-rays [12]. Furthermore, the material was re-evaluated by one of the authors blinded to participant status and treatment. Several studies report a catabolic effect of PTH on cortical bone and an anabolic effect on cancellous bone [24, 25, 27]. This is consistent with normal BMD in cancellous bone, i.e. lumbar spine, and decreased BMD in the forearm in clinically detected pHPT [22].

There is a risk of introducing a type 1 error when performing multiple tests. However, all analyses were prespecified according to our hypothesis. Overall, we used a limited number of statistical tests and the biological plausibility of our findings would argue against a type 1 error as an explanation for our findings. Our results also extend the results found in previous studies with more severe pHPT.

Altogether 14 cases and 20 controls were on HRT at various times. Presumably this would lower serum calcium marginally and possibly have a positive effect on BMD at the 5-year follow-up [5]. However, the group analyses were similar after excluding HRT-treated patients or controls. Furthermore, vitamin D status was not evaluated, which should be of interest in secondary HPT due to renal insufficiency. Our patients did not suffer from apparent renal insufficiency since serum creatinine was normal in all but four cases with values slightly above the reference range. Indeed, parathyroid histopathology in the operated cases closely resembled findings in conventional pHPT series [13, 28]. In parallel, renal impairment as a cause for bone loss is unlikely, as mentioned above. Also, serum PTH was only marginally elevated compared with the much higher levels encountered in secondary HPT.

The present series demonstrated decreased BMD in the lumbar spine and femoral neck in mild pHPT, which is consistent with findings in other series with various ranges including much higher serum calcium [20, 29, 30]. Parathyroidectomy increased BMD in the lumbar spine; the discrepancies with the controls were eliminated, and the decreased BMD of the femoral neck, seen in untreated mild pHPT, could be minimized. It is noteworthy that cases below 67 years of age also demonstrated increased BMD in the femoral neck postoperatively. Serum calcium had an inverted correlation with BMD, explaining 7% of the BMD value after adjustment for weight. The latter finding reduces calcium as a predictor of bone loss in mild pHPT. In fact, patients with truly mild pHPT and serum calcium <2.60 mmol L−1 also had a T-score of −2.5 SD or lower. This finding corroborates notions on the existence of bone loss early and in very mild stages of pHPT [29, 31, 32] and underlines the potential gain from active treatment in mild pHPT in postmenopausal females as well [20, 29, 33].

Acknowledgements

  1. Top of page
  2. Abstract.
  3. Background
  4. Method
  5. Results
  6. Discussion
  7. Conflict of interest statement
  8. Acknowledgements
  9. References

We thank the staff of the Osteoporosis Clinic, Department of Internal Medicine, Uppsala University Hospital, for taking care of patients and controls in a professional manner.

References

  1. Top of page
  2. Abstract.
  3. Background
  4. Method
  5. Results
  6. Discussion
  7. Conflict of interest statement
  8. Acknowledgements
  9. References
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