Bone disease blood test may help predict AS radiographic progression
Alkaline phosphatase blood test could reveal bone-specific biomarkers in AS
A blood test for bone disease that measures the levels of an enzyme called alkaline phosphatase (ALP) may predict disease progression of ankylosing spondylitis five years before abnormalities can be observed on radiographic exams, according to a new study.
“This is not only useful for finding bone-specific biomarkers that predict radiographic progression but also for representing a period of active bone metabolism that should be addressed in clinical and experimental studies evaluating the radiographic progression of AS,” investigators wrote.
The study, “Association between changes in serum alkaline phosphatase levels and radiographic progression in ankylosing spondylitis,” was published in the journal Scientific Reports.
Radiographic changes can stem from inflammation, repair, new bone formation
AS is a type of arthritis characterized by stiffness of the spine and the sacroiliac joints — where the base of the spine meets the pelvis. Inflammation and new bone formation in the spine contribute to joint stiffness and pain.
Radiographic changes in AS are due to a sequence of events that include inflammation, repair, and new bone formation in the spine. Such changes may happen before noticeable alterations can be seen on radiographs.
Although previous studies assessed changes in inflammatory markers that precede radiographic progression, “no studies have evaluated the relationship between the timing of changes in bone metabolism and radiographic progression in patients with AS,” according to the researchers. Bone metabolism is a dynamic process of bone formation and bone resorption.
To determine this relationship, researchers in South Korea evaluated the medical records of 1,122 AS patients, followed up at a single center from January 2001 to December 2018. Most patients visited the outpatient department approximately every six months and underwent spine examinations at least every two years.
Patients had a mean age of 32 years, were mainly men (88.4%), and were followed up for a mean of 8.2 years. During patient follow-up, the researchers collected data for inflammatory markers, disease activity, and radiographs.
The participants were evaluated a mean 4.58 times using the modified stoke ankylosing spondylitis spinal score (mSASSS) — a scoring method to quantify chronic structural changes on radiographs — with an average of 2.34 years between evaluations. Generally, mSASSS increased in most patients, although scores at the study’s start were highly variable among patients.
Blood levels of ALP — a potential marker of bone turnover, according to the scientists — were obtained for up to eight years in three-month intervals. Bone turnover is the process of bone resorption followed by replacement with new bone.
ALP levels before spinal radiographic changes linked to disease progression
ALP levels in the blood at five years and three months before spinal radiographic changes were significantly correlated with AS progression (mSASSS) observed in radiography.
The researchers noted that this is a longer period than that defined by C-reactive protein, a marker of inflammation, and radiographic progression, which correlated with the two-year interval of spinal cord examinations.
This indicated that “long-term prospective clinical and experimental studies of [more than five] years are required for biomarker discovery or therapeutic research on AS radiographic progression,” the researchers wrote.
However, the study has some limitations, including the fact that ALP can be produced by other organs. The study also did not consider other factors that may affect bone turnover such as osteoporosis (weak, brittle bones), nor did it account for drugs that might affect bone metabolism.
Longer studies of bone metabolism are needed in the future, the team noted, as well as determinations of potential therapies for radiographic progression in AS.