|Year : 2022 | Volume
| Issue : 1 | Page : 7-12
Parathyroid hormone predicts radial bone loss in healthy Nigerian adults
Ayotunde Oladunni Ale1, Akintayo S Oguntona1, Olufunke O Adeleye1, Olufunmilayo O Adeleye2, Taiwo O Afe1, Olusola L Adeyemo1
1 Department of Medicine, Obafemi Awolowo College of Health Sciences, Olabisi Onabanjo University/Teaching Hospital, Ogun State, Nigeria
2 Department of Medicine, Endocrinology Unit, Lagos State University Teaching Hospital, Ikeja, Lagos, Nigeria
|Date of Submission||07-Dec-2021|
|Date of Decision||23-Apr-2022|
|Date of Acceptance||24-Apr-2022|
|Date of Web Publication||20-Jul-2022|
Dr. Ayotunde Oladunni Ale
Department of Medicine, Obafemi Awolowo College of Health Sciences, Olabisi Onabanjo University/Teaching Hospital, Sagamu, Ogun State
Source of Support: None, Conflict of Interest: None
Objective: The correlation between bone mineral density (BMD) and bone markers is well studied in postmenopausal women and elderly men. However, related literature on healthy adults is scarce. This study determined the correlation between parathyroid hormone (PTH), BMD of the left distal radius, and other biochemical markers in apparently healthy Nigerian adults. Methods: This research included 80 (28 males/52 females) healthy participants between 22 and 50 years of age (32.10 ± 5.8 years) who met the inclusion criteria. All the participants were recruited by a systematic random sampling. Interview questionnaires were used to supplement clinical data and anthropometric measures. Fasting samples were analyzed for calcium, inorganic phosphorus, 25-hydroxyvitamin D (25[OH]D), PTH, osteocalcin (OC), alkaline phosphatase, and 24-h calcium excretion. The left distal radius BMD was examined using dual-energy X-ray absorptiometry. The data were statistically analyzed, and the significance level was set at <0.05. Results: It was found that PTH was inversely correlated with left distal radius BMD/z-score (P = 0.004). It showed positive and negative trends with serum-adjusted calcium and inorganic phosphorus (P = 0.09 and P = 0.07, respectively). Neither the OC nor 24-h calcium excretion correlated with PTH (P > 0.05). The OC was inversely correlated with BMD (P = 0.003), but not with 24-h urinary calcium excretion (P > 0.05). None of the participants had osteoporosis. Regression analysis showed that PTH and OC predict radial bone density in participants (P < 0.05). Conclusion: Higher PTH levels correlate with lower left distal radius BMD in apparently healthy participants.
Keywords: Biochemical biomarkers, bone mineral density, left distal radius, parathyroid hormone
|How to cite this article:|
Ale AO, Oguntona AS, Adeleye OO, Adeleye OO, Afe TO, Adeyemo OL. Parathyroid hormone predicts radial bone loss in healthy Nigerian adults. Bangladesh J Endocrinol Metab 2022;1:7-12
|How to cite this URL:|
Ale AO, Oguntona AS, Adeleye OO, Adeleye OO, Afe TO, Adeyemo OL. Parathyroid hormone predicts radial bone loss in healthy Nigerian adults. Bangladesh J Endocrinol Metab [serial online] 2022 [cited 2023 Feb 5];1:7-12. Available from: https://www.bjem.org/text.asp?2022/1/1/7/351525
| Introduction|| |
Parathyroid hormone (PTH) is a peptide with 84 amino-acid sequences. The low level of calcium in the blood causes the parathyroid gland to secrete PTH. Its key role is to control calcium and phosphate metabolism. Thus, its clinically normal range may influence the bone health. The hormone affects both bones and nonskeletal tissues such as the kidneys and the intestine. In the kidney, it promotes the formation of calcitriol, also known as active Vitamin D, and then functions with calcitriol to regulate calcium and phosphate. Thus, it is considered a clinical indicator of serum Vitamin D bioactivity. In addition, by increasing calcium reabsorption in the distal convoluted tubule and collecting duct present in the kidneys, the PTH enhances serum calcium levels, thereby decreasing phosphate reabsorption in the proximal convoluted tubule. Thus, it further helps in increasing the amount of calcium by decreasing the available phosphate ions to form insoluble salts of calcium.
PTH exerts its action on the bones via both direct and indirect processes. Its direct action includes stimulating the osteoblasts to enhance receptor (receptor activator of NF-κB-RANK) expression for its ligand (nuclear factor kappa-B ligand-RANKL), thus inducing osteoblasts to differentiate into osteoclasts. Osteoblasts secrete osteoprotegerin that competitively binds to RANKL to inhibit both the differentiation and the function of osteoclasts. Osteoclasts function in bone remodeling by causing bone resorption and deterioration of hydroxyapatite and various other organic materials and also by releasing calcium ions into the blood. The hormone inhibits the secretion of osteoprotegerin to allow selective differentiation of osteoclasts. A continued secretion of PTH results in a condition termed hyperparathyroidism, which results in bone resorption. In contrast, the hormone exerts positive effects or anabolic actions on bone volume and structure at low levels. These effects are exerted by the direct action on osteoblasts and indirect action via the activation of skeletal growth factors. Moreover, PTH causes inhibition of sclerostin by activating the Wnt-β signaling pathway that is involved during osteogenesis. Furthermore, PTH increases the proliferation and differentiation of osteoblasts and prevents their apoptosis.
Bone is considered a dynamic tissue that frequently undergoes remodeling and turnover to balance bone synthesis and resorption. Assays for bone turnover can be used to assess bone disorders and, thus, their treatment. Osteocalcin (OC) and urinary calcium excretion serve as markers for bone-forming osteoblastic activity and bone resorption osteoclastic activity, respectively. OC is a late marker, has short half-life, and is unstable. In patients with osteoporosis, excretion of urinary calcium is an inexpensive and effective method to study bone turnover. The potential of these biomarkers in predicting bone loss, especially in older individuals, is well established.,,, A study reported the efficacy of using bone turnover markers in predicting alterations in bone mineral density (BMD) in middle-aged and elderly men of Europe. Those men with huge bone turnover had an increased risk of loss of hip bone. However, a similar role of these biomarkers in healthy younger adults is yet to be established.
Vitamin D alters the bone health; a study in Caucasians demonstrated a firm association between BMD and Vitamin D. Similarly, a Korean study in participants ≥50 years revealed a relatively lower amount of Vitamin D intake and concluded that Korean adults should increase their Vitamin D intake to improve their BMD. However, Kota et al. reported an absence of a direct association between BMD and 25-hydroxylvitamin D levels and an inverse relation between intact PTH and 25-hydroxylvitamin D levels in a cohort of Indian patients. A study of women in Saudi Arabia reported insufficient calcium supplements and Vitamin D consumption and advised women to improve their nutrition.
A study reported higher PTH levels in individuals with low BMD, especially in weight-bearing areas such as the hip. Moreover, hyperparathyroidism increases the risk of several complications, such as kidney stones. Numerous examinations have emphasized an association among the elevated PTH levels and lower BMD in the elderly,,, middle-aged women, postpartum women, and women with primary hyperparathyroidism., However, only few research groups have studied the association among healthy adult Nigerians. For example, a study on young Nigerian adults reported their increased susceptibility to bone fractures due to hyperthyroidism. Another study reported the increased incidence of thyroid disorders among young Nigerians but with no details on the etiology. To bridge this gap, the present study on healthy adult Nigerians evaluated the affinity among PTH, BMD, and other bone-related markers.
| Methods|| |
Design and setting
This cross-sectional study was conducted at the endocrine unit of a tertiary hospital in Southwest Nigeria. The study was carried out in accordance with the principles of the Declaration of Helsinki. Study approval was granted by the Ethics Committee of Lagos State University Teaching Hospital, Ikeja, Lagos, Nigeria. All participants signed informed consent before the commencement of research.
Eighty healthy participants, aged between 22 and 50 years, were recruited using a systematic random sampling. Healthy volunteers were recruited from among hospital staff and healthy relatives of patients who visited the hospital. Exclusion criteria were participants with any disease including cardiovascular disease, liver disease, renal disease, parathyroid disease, thyroid disorder, previous fractures, and bone disease; smoking or alcohol intake; menopause; amenorrhea; or any drug use.
Interviewer-administered questionnaires were employed to acquire demographic information. Height, weight, and waist circumference (WC) of the participants were measured in accordance with the standardized methods. Body mass index (BMI) of all participants was estimated by the formula of weight (kilograms)/the square of height (meter2).
Under sterile conditions, samples of fasting blood were collected to conduct clinical and hormonal studies. Urine samples were obtained to assess calcium and creatinine levels. Calcium, serum albumin, phosphorus, alkaline phosphatase (ALK), and creatinine concentrations were determined using a timed endpoint method, bromocresol green albumin assay, vanadate-molybdate method, Hausamenetal method, and modified Jaffe method, respectively. The estimated glomerular filtration rate (eGFR) was determined using the Cockcroft–Gault equation.
Analyses of 25-hydroxyvitamin D (25[OH]D), OC (1-43/49), thyroid function tests, and intact PTH levels were determined by an enzyme-linked immunosorbent assay method (ELISA). ELISA kits procured included 25-hydroxyvitamin D kit (AC-57F1, LOT 11971) from Immunodiagnostic Systems Holdings Limited,10 Didcot Way, Boldon Business Park, Tyne & Wear, NE35 9PD, United Kingdom; Osteocalcin kits (43-OSNHU-E01, LOT NO-D852) from ALPCO Immunoassay, 26-G Keewaydin DRIVE, Salem, NH 03079, USA and Intact Parathyroid kits (cat # 1735Z) from Diagnostic Automation, INC., Calabasas, California 91302, USA. The assay results were read off using a Thermo Fisher Multiskan EX microplate reader after following the manufacturer's protocol.
Bone mineral density determination
Lunar PIXI peripheral densitometer using dual-energy X-ray absorptiometry (DXA) technique was employed in the measurement of the left distal radius (lower-third) BMD. This is because PTH dysfunction preferentially affects cortical bone (forearm) than cancellous (spine), and the cortical bone loss is not easily reversible. BMD is expressed as exact values in g/cm2 and as z-score, which represent the BMD value normalized for age- and sex-matched reference population. In adults <50 years, the International Society for Clinical Densitometry (ISCD) criteria are used for the definition of BMD and z-score <−2 as osteoporosis and normal as >2.
Definition of terms
- Vitamin D deficiency is defined by 25(OH)D by <25 nmol/L (<10 ng/mL), low normal (insufficiency): 25–50 nmol/L (11–20 ng/mL), and adequacy >50 nmol/L (>20 ng/mL)
- Elevated PTH is defined by PTH > 6.9 pmol/L
- Osteoporosis is defined by the ISCD criteria as z-scores <2.
Statistical computational was conducted using a software package SPSS version 21.0; IBM (IBM SPSS Statistics for Windows, Version 21.0. Armonk, NY: IBM Corp.USA). The results were represented as mean, standard deviations, and proportions (frequencies). Pearson's correlation was used to examine the relationship between PTH and BMD and other bone-related markers. Binary logistic regression was used to determine the predictor of BMD. The significance level (P-value) was set at <0.05.
| Results|| |
The present study analyzed 80 healthy participants. The mean age of the participants was 32.1 ± 5.8 years, with 28 males and 52 females. The mean WC of the population was 79.60 ± 16.01 cm, and the mean BMI was 26.31 ± 4.0 kg/m2. The study found a mean intact PTH level of 6.33 ± 0.49 pmol/L, mean 25(OH)D level of 51.5 ± 15.45 nmol/L, and mean BMD of 0.57 ± 0.07 g/cm2 with a mean z-score of 0.2 ± 1.05. None of the participants had osteoporosis or Vitamin D deficiency or elevated PTH. Other clinical, biochemical, and hormone indices are shown in [Table 1].
Correlation analysis of PTH and other parameters
Age, body mass index, and waist circumference
As expected, PTH was not significantly associated with the age of the participants (r = 0.06, P = 0.7), adiposity indices such as body mass index (r = 0.02, P = 0.86), and WC (r = 0.2, P = 0.2).
Albumin-adjusted calcium and serum phosphorus
A positive and negative trend of PTH was observed with albumin-adjusted calcium (r = 0.26, P = 0.09) and inorganic phosphorus (r = −0.3, P = 0.07), respectively.
Bone turnover markers
No correlation between PTH and OC (r = −0.13, P = 0.4) or PTH and calcium urinary excretion (mg/24 h) (r = −0.21, P = 0.2) was observed.
25-Hydroxyvitamin D status
It was found that 25(OH)D did not significantly correlate with PTH (r= −0.03, P = 0.98). None of the participants had vitamin deficiency. However, 75% had insufficiency, and only 25% with normal levels. With mean Vitamin D insufficiency and normal Vitamin D levels (42.1 ± 6.2 nmol/L vs. 61.6 ± 4.3 nmol/L; P = 0.04).
No correlation was found between PTH and ALK (r = 0.13, P = 0.43) or ALK and 25(OH)D (r = −0.6, P = 0.5).
Left distal radius bone mineral density
There was an inverse correlation between PTH and left distal radius BMD/z-score BMD (r = −0.50, P = 0.004).
Kidney function (estimated glomerular filtration rate)
A significant inverse correlation was observed between PTH and eGFR (r = −0.4, P = 0.01).
A significant correlation was observed between PTH and thyroxine (FT4; r = 0.4, P = 0.01), but not to triiodothyronine (FT3; r = 0.04, P = 0.83) or thyroid-stimulating hormone (TSH; r = −0.12, P = 0.47).
Correlation of bone mineral density with biochemical bone markers
OC was significantly and inversely correlated with BMD/z-score (r = −0.46, P = 0.003). However, neither 24-h urinary calcium (r = −0.01, P = 0.9) nor Vitamin D (r = −0.18, P = 0.3) correlated with BMD/z-score.
Binary logistic regression analysis showed that the likely predictors of radial BMD/z-score were OC and PTH, as shown in [Table 2].
|Table 2: Regression analysis between bone-related parameters and radial bone mineral density/z-score|
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| Discussion|| |
This study investigated the relationship between PTH and left distal radius BMD (composed mainly of cortical bone) using the Lunar PIXI Densitometer machine and other bone-related bone markers in healthy adult Nigerians (mean age was 32.10 years with normal renal function). Only a few studies have determined whether PTH is associated with skeletal parameters in Nigerians, especially in the Sub-Saharan region, owing to the scarcity of DXA scan – the recommended method for measuring BMD – coupled with the high cost of PTH assays with few laboratories equipped to conduct hormonal assays. The current study revealed that PTH was inversely correlated with left distal radius BMD with positive and inverse trends observed in serum calcium and phosphorus levels, respectively. No association was found between PTH and skeletal parameters of 25(OH)D and biochemical bone markers. Furthermore, BMD was significantly correlated with the marker of bone synthesis, as was observed. However, there was no correlation with the bone resorption marker.
Similar to a previous study, the present study found that left distal radius BMD showed no significant correlation with 25(OH)D. This could lay credence to the finding of higher BMD despite a lower Vitamin D status in African–Americans in contrast to their Caucasian counterparts, which showed an inverse relation. In the current study, most participants had low normal levels of Vitamin D (Vitamin D insufficiency) with no deficiency and no osteoporosis, a finding that could likely account for this relationship. In contrast to the above reports, another study in the Saudi population reported no association between Vitamin D deficiency and low BMD among males and females of all age groups.
The current study found that PTH, Vitamin D, and other bone biomarkers were not significantly correlated. This finding is an indication that the 25(OH)D threshold at which PTH and bone markers are secreted in Nigerians is lower since a higher BMD and lower Vitamin D status have been reported in the blacks. The findings of the current study support those of the report by Sai et al., who found that 25(OH)D, PTH, and bone markers were disassociated. The plausible explanation by Reid suggested that for 25(OH)D between 30 and 50 nmol/L, the PTH is compensated for low Vitamin D levels without increasing bone resorption. A tightly controlled feedback loop mechanism regulates PTH and Vitamin D levels; PTH stimulates Vitamin D synthesis in the kidneys; and Vitamin D regulates the secretion of PTH via the negative feedback loop. PTH exerts its effects by increasing the circulating levels of calcium and decreasing phosphate, whereas Vitamin D exerts a stimulatory effect on both calcium and phosphate.
We observed that bone formation marker, OC, a measure of osteoblastic activity, was significantly and inversely associated with left distal radius BMD in Nigerian adults. This finding is in accordance with other studies that reported an increase in OC associated with decreased BMD., The 24-h calcium excretion rate, considered a resorption marker, did not correlate significantly with BMD. This finding confirmed previous studies of the absence of correlation between BMD and bone resorption markers.,
Similar to the findings of previous studies that reported a graded decrease in BMD with higher levels of PTH in middle-aged to elderly people, and younger healthy populations, the current study reported a significant correlation between PTH and left distal radius BMD. Rubin et al. reported similar significant correlations between BMD and bone markers, PTH and OC levels in patients with hyperparathyroidism. Collectively, these results may suggest that parathyroid hormone and serum osteocalcin are markers of bone loss, whereas vitamin D could be considered as a marker only beyond a specific bone loss threshold. Therefore, the impact of lower 25(OH)D levels and deficiency on the graded decrease in BMD needs to be researched.
Our study has some limitations. We did not study the effects of PTH on other vertebral sites. Future studies should examine the impact of PTH, 25(OH)D, and bone markers on BMD at the lumbar spine and femoral neck in Nigerians. Furthermore, a larger sample size may be beneficial to confirm the relationship between PTH levels, 25(OH)D levels, and BMD in adult Nigerians.
| Conclusion|| |
PTH is crucial for maintaining calcium and phosphate metabolism, including BMD, and regulating Vitamin D bioactivity. Although numerous studies are available that report the relationship between bone markers and BMD in postmenopausal women and elderly men, literature on healthy Nigerian adults is scarce. The current study reports an inverse correlation between PTH and left distal radius BMD, without an association with other bone biomarkers. However, a trend was observed between PTH and adjusted-serum calcium and inorganic phosphorus. These findings suggest PTH and serum OC as potential markers for BMD and bone loss. In contrast, Vitamin D may be reflective of BMD only beyond a certain bone loss threshold. It would be interesting to further investigate the effect of PTH on other vertebral sites in adult Nigerians.
The manuscript reviewed by Thomas V Sanchez is well appreciated.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2]