Abstract
Methods
A retrospective study was conducted at three Palestinian healthcare centers between February and December2023. Targeting RA patients of both sexes and all ages, the clinical characteristics of 397 patients werecategorized using a stratifi ed sampling technique. Data were retrieved from each center’s respective archivemodalities. An adjusted multiple logistic regression model was utilized to test the association between1,25(OH)
2
VD
3
and Parathyroid levels with musculoskeletal pain severity. A p-value less than 0.05 was consideredstatistically signifi cant. The Kolmogorov-Smirnov test was utilized to test the normality of continuous variabledistribution.
Results
Many patients fulfi ll criteria for other conditions, with slow disease progression noted, despite correct RAdiagnosis. Pain severity correlated with defi cient 1,25(OH)
2
VD
3
(1.745 OR, P-value:0.05) and high PTH levels (PTH:1.579 OR, P-value:0.027). Commonly reported pains include lower back, knees, cervical, and upper back areas.Muscular stiffness and bone tenderness are prevalent, with 41.03% reporting severe pain. Increased agecorrelates with severe pain (OR:1.53, P-value:0.015). Likewise, Type 2 Diabetes mellitus shows a signifi cantpositive association (OR:0.741, P-value:0.017). Despite the lack of signifi cant associations, the high prevalence ofsmoking (47.1%) and hypertension (58.9%) requires intervention. Radiological reporting is unclear in 63.22% ofcases, with 'bone spurs' commonly utilized. Additionally, 93.9% have low ionized calcium levels. Other lab resultsmostly fall within normal ranges, emphasizing the complexity of diagnosis and suggesting the importance ofthorough radiological investigations and laboratory assays.
Conclusions
We recommend expanding MEPS criteria to include other conditions, highlighting the signifi cant associationsbetween 1,25(OH)
2
VD
3
defi ciency, HPT, advanced age, and Type 2 Diabetes mellitus with musculoskeletal pains indiagnosed RA cases.
Background
The musculoskeletal system is a core element that infl uences many human health aspects. Changes in a plethoraof crucial biochemical elements can signifi cantly alter the clinical manifestations of this system, primarilymusculoskeletal pains. A novel yet understudied syndrome that tackles the intertwined relationship between themusculoskeletal system and alterations in the body’s biochemical stores is the Middle East Pain Syndrome(MEPS). Despite the lack of enough evidence to formulate a consensus on its defi nition, MEPS can be defi ned as acombination of chronic Vitamin D
3
defi ciency, possible hyperparathyroidism (HPT), and Fibromyalgia in MiddleEastern patients that do not fulfi ll the criteria of Rheumatoid Arthritis (RA) (
1
).
Alterations in the physiological levels and biochemical processes regarding 1,25(OH)
2
VD
3
is heavily tied tochanges in the parathyroid hormone (PTH) levels. PTH is involved in bone resorption and the utilization of calcium
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in the bloodstream via binding to the osteoclasts’ receptors. 1,25(OH)
2
VD
3
defi ciency can lead to HPT,manifesting as increased levels of the PTH. HPT is categorized into primary, secondary, and tertiary HPT. PrimaryHPT is a metabolic condition in which hypercalcemia and typical/hyperparathyroidism occur due to the benignovergrowth of one or more parathyroid glands (
2
). In contrast, secondary and tertiary HPT are induced by externalstimuli. Secondary hyperparathyroidism (SHPT) is the body’s attempt to maintain calcium homeostasis inresponse to hypocalcemia by increasing secreted PTH. The main pathological background to SHPT is chronickidney disease, in which the renal inability to yield adequate amounts of 1,25(OH)
2
VD
3
from 1,25(OH)
2
VD
2
ultimately leads to the inability of the body to excrete phosphate. Consequently, insoluble phosphate-calciumcomplexes form and hinder the utilization of calcium. Lastly, tertiary HPT is hypercalcemia within the context ofautonomous over-secretion of PTH by hyperplastic parathyroid glands due to chronic secondary HPT (
3
).
The Endocrine Society’s clinical practice guidelines outline those levels of 1,25(OH)
2
VD
3
above 30 ng/ml areoptimal, less than or equal to 20 ng/ml as a defi ciency, with levels between 21–29 ng/ml as insuffi ciency (
4
).1,25(OH)
2
VD
3
defi ciency increases the risk of fractures, pseudoarthrosis, and bony lesions (
1
,
5
). 1,25(OH)
2
VD
3
defi ciency can occur due to malabsorption conditions, renal failure, reduced nutritional intake, or inadequate sunexposure. Consequently, hypocalcemia and subsequent HPT may occur (
6
). According to Elbeialy et al., thecommon clinical manifestations of HPT and 1,25(OH)
2
VD
3
defi ciency include muscle cramps, bone pain, FMS,juxta-articular erosions, tenosynovitis, periarteritis, and pericapsural calcifi cation (
1
). Moreover, combined HPTand 1,25(OH)
2
VD
3
defi ciency causes musculoskeletal pain due to hypocalcemia-induced osteoporosis andcalcium pyrophosphate deposition-induced degenerative arthritis and muscular weakness (
7
).
Healthcare professionals continue to diagnose patients with arthritic conditions, such as RA, despite their failureto fulfi ll the entirety of their criteria. Consequently, patients experience slight improvement upon adhering to theirtreatment plans. MEPS is proposed as an HPT-induced RA-mimicking syndrome (
1
). Furthermore, MEPS ispostulated to be correlated with cadmium toxicity, a proposed cause of chronic 1,25(OH)
2
VD
3
defi ciency in theMiddle East. Cadmium can be deposited in the kidneys, the leading site of converting 25(OH)
2
VD
3
to1,25(OH)
2
VD
3
, leading to dysfunctions in the mitochondrial electron transport chain and NADPH oxidase.Subsequently, reactive oxygen species form and induce oxidative damage on epithelial cells, manifesting in adecline in kidney functions (
8
–
10
).
Despite the novel scientifi c evidence proposed by Elbeialy et al. regarding MEPS, there needs to be reportedevidence investigating the possibility of adding other orthopedic and rheumatologic conditions to the defi nition ofMEPS, which focused on Fibromyalgia only. Thus, this paper aims to shed light on such a possibility, hoping toincrease awareness among clinical practitioners and the general population regarding MEPS. Moreover, this papermay have an integral impact on clinical practice guidelines in orthopedics and rheumatology. This paper alsoinvestigates the prevalence, risk factors, severity, and variation in Palestinian patients consideringmusculoskeletal pains

Title

research squre

Publisher

Mohammad M Jaber

Publisher Country

United States of America

Publication Type

Prtinted only

Volume

--

Year

2024

Pages

--