Bone health in Graves’ disease: a comparison of black and white South African women
| dc.contributor.advisor | Mollentze, W. F. | |
| dc.contributor.advisor | Pettifor, John M. | |
| dc.contributor.author | De Lange, Willem | |
| dc.date.accessioned | 2021-03-25T09:23:19Z | |
| dc.date.available | 2021-03-25T09:23:19Z | |
| dc.date.issued | 2019 | |
| dc.description.abstract | Objectives: The negative effects of thyrotoxicosis on bone health in white populations have been widely studied. In non-South African black populations, it has been showed that the skeleton is protected against the negative effects of other endocrinopathies, for e.g.: hyperparathyroidism. The aim of the study was to determine whether black South African women are also protected against the detrimental effects of Graves’ disease (GD)? Background and motivation: The detrimental effects of thyrotoxicosis on bone health has been known for more than a century. In white females, thyrotoxicosis has been shown to increase the rate of bone resorption along with bone formation. However, the rate of bone formation is inadequate to compensate for bone resorbed, leading to a net loss of bone volume. This negatively impacts on the structural integrity of bone with an increased fracture risk. Little is known about the effect of thyrotoxicosis on bone health in black African-, and especially black South African women. Ethnic differences in bone metabolism and fat distribution do exist between black and white South African women. Dual-energy X-ray absorptiometry (DXA) studies have shown that the bone mineral density at the lumbar spine of healthy premenopausal black South African women, is equal or lower than that of their white counterparts. The bone mineral density of postmenopausal black- and white women at the lumbar spine is comparable. Vertebral fracture risk of the lumbar spine is equal for black- and white South African women. Significant differences in femoral bone density do exist when black and white South African women are compared. Black South African women have a greater bone mineral density at the femur neck site. Histomorphometric and radiometric differences between these two ethnic groups may explain the lower incidence of femoral fragility fractures in the black population. Black South African women, when compared to their white counterparts, have thicker and less porous cortices as well as thicker trabeculae. These micro architectural differences could explain the decreased number of fractures seen in black females when compared to white females. There are also ethnic differences in the abdominal adipose tissue depot distribution. White men and women have increased abdominal visceral adipose tissue and decreased subcutaneous adipose tissue when compared to black men and women. Thyrotoxicosis has detrimental effects on bone metabolism and bone structure in white women. These effects can lead to an increased risk of fracture that persists even after normalization of the bone mineral density. Study design: This was a prospective exploratory and comparative study. Methods: A convenience sample of 40 consecutive and consenting black female patients (age ≥ 25 and ≤ 65 years) and 20 consecutive and consenting white female patients (age ≥ 25 and ≤ 65 years) with confirmed GD referred to the Endocrine service at Universitas Hospital were recruited for the study. Patients were matched with 40 black and 20 white healthy control females according to age (± 5 years), body mass index (BMI) and seasonality. Black- and white South African women suffering from GD were compared with each other at baseline, 6- and 12 months according to pre-determined objectives. Women suffering from GD were also compared with healthy controls from the same ethnic group. This comparison was performed to rule out effects of ethnicity versus effects of GD on bone health. The main objectives included differences in biochemical markers, bone mineral density and body composition. Histomorphometric data on the effect of GD on bone in white ethnic groups has been published before. Therefore, bone histomorphometry was only performed in black women suffering from GD to ascertain whether ethnic differences do exist. Results: In this prospective study, 39 black women and 20 white women with newly diagnosed GD were included. The median parathyroid hormone (PTH) level of black women suffering from GD was suppressed and significantly lower when compared to white patients (p = 0.04). The suppressed PTH in black patients were accompanied by increased serum calcium levels. The markers of bone formation as well as bone resorption were increased in both patient groups. The median urine deoxypyridinoline (DPD) to creatinine ratio (Urine DPD), a marker of bone resorption, was significantly higher in black women suffering from GD compared to white patients (p = 0.026). Although the median 25-hydroxyvitamin D (25(OH)D) level of black patients with GD was lower compared to their white counterparts and suppressed below the lower limit of the laboratory threshold, it did not differ significantly. The median 1,25dihydroxyvitamin D (1,25(OH)2D) levels of black- and white patients were normal and not different. A marker of inflammation, tumour necrosis factor alpha (TNFα), was significantly higher in black patients compared to white patients (p = 0.022) while the other markers included, interleukin 6 (IL-6) and C-reactive protein (CRP), did not differ. The median insulin-like growth factor 1 (IGF-1) levels of both patient groups were lower compared to healthy controls. The median IGF-1 of black patients was significantly lower compared to that of healthy black controls (p = 0.001). The same was observed in white patients and – controls with white patients having a significantly lower median IGF-1 level (p = 0.05). There was no difference between the two patient groups. The actual bone mineral density (BMD) of white patients at the left femoral neck was significantly lower compared to black patients at baseline (p = 0.033). This difference was not observed between white patients and –controls. The BMD at the left forearm distal 3rd was lower in black patients compared to white patients (p = 0.049). Although the same pattern was observed when comparing the median Z-scores at baseline, it did not reach significance. The median Z-score at the left total hip of white patients were significantly lower when compared to white controls (p = 0.039). A greater proportion of black patients had a median Z-score of the lumbar spine ≤ -2.0 compared to white patients (p = 0.028). The difference observed of actual BMD at the left femoral neck between black- and white patients at baseline was maintained at 6- and 12 months after therapy. The difference at the left forearm distal 3rd disappeared at months 6 and 12. The actual BMD of white patients at the right femoral neck was significantly lower at 12 months compared to black patients (p = 0.030). The body composition of both black- and white patients were comparable at baseline. However, the percentage change in body mass index (BMI) did differ significantly from 0-6 and 0-12 months between the two patient groups. Black patients had a significantly higher percentage increase in BMI at 0-6 months (p = 0.042) and 0-12 months (p = 0.01) compared to white patients. The body composition of white patients and –controls did not differ significantly at baseline, 6- and 12 months. Although the body composition of black patients and –controls were comparable at baseline, black patients had a significant increase of especially fat tissue after treatment. This is confirmed by a significantly higher fat mass index (FMI) found in black patients at 12 months compared to controls (p = 0.011). The bone histomorphometry revealed a state of accelerated bone turnover, predominant stimulation of bone resorption and histological evidence of demineralization as evidenced by abundant osteoid on histology. Conclusions: Ethnic differences between black- and white South African women suffering with GD were shown. Black South African women are not protected against detrimental skeletal effects of GD. It is hoped that this study will contribute to a better understanding of bone health in the South African population in general, but especially those patients with GD. It is also envisioned that this may lead to improved management of patients once thought to be protected against the skeletal complications of GD. Further South African research is warranted. | en_ZA |
| dc.description.sponsorship | University of the Free State, Research Development | en_ZA |
| dc.identifier.uri | http://hdl.handle.net/11660/10987 | |
| dc.language.iso | en | en_ZA |
| dc.publisher | University of the Free State | en_ZA |
| dc.rights.holder | University of the Free State | en_ZA |
| dc.subject | South Africa | en_ZA |
| dc.subject | Thyrotoxicosis | en_ZA |
| dc.subject | Graves’ disease | en_ZA |
| dc.subject | Bone mineral density | en_ZA |
| dc.subject | Histomorphometry | en_ZA |
| dc.subject | Fracture risk | en_ZA |
| dc.subject | Body composition | en_ZA |
| dc.subject | Thesis (D.Med.Sc. (Internal Medicine))--University of the Free State, 2019 | en_ZA |
| dc.subject | Hypothyroidism | en_ZA |
| dc.subject | Women -- South Africa -- Thyrotoxicosis | en_ZA |
| dc.title | Bone health in Graves’ disease: a comparison of black and white South African women | en_ZA |
| dc.type | Thesis | en_ZA |