Possible role of bone turnover markers in the diagnosis of adult hypophosphatasia

被引：1

作者：

Bertoldo, Francesco ^{[1
]}

Tripepi, Giovanni ^{[2
]}

Zaninotto, Martina ^{[3
]}

Plebani, Mario ^{[3
]}

Scillitani, Alfredo ^{[4
]}

Varenna, Massimo ^{[5
]}

Crotti, Chiara ^{[5
,6
]}

Cipriani, Cristiana ^{[6
]}

Pepe, Jessica ^{[6
]}

Minisola, Salvatore ^{[6
]}

Pugliese, Flavia ^{[4
]}

Guarnieri, Vito ^{[7
]}

Baffa, Valeria ^{[8
]}

Torres, Marco Onofrio ^{[8
]}

Zanchetta, Francesca ^{[8
]}

Fusaro, Maria ^{[9
]}

Rossini, Maurizio ^{[10
]}

Brandi, Maria Luisa ^{[11
]}

Egan, Colin Gerard ^{[12
]}

Simioni, Paolo ^{[8
]}

Arcidiacono, Gaetano Paride ^{[8
]}

Sella, Stefania ^{[8
]}

Giannini, Sandro ^{[8
]}

机构：

[1] Univ Verona, Bone Metab & Osteoncol Unit, I-37129 Verona, Italy

[2] Osped Riuniti Reggio Calabria, Natl Res Council CNR, Inst Clin Physiol IFC Clin Epidemiol Renal Dis & H, I-89124 Reggio Di Calabria, Italy

[3] Univ Padua, Dept Med, Lab Med Unit, I-35128 Padua, Italy

[4] IRCCS, Casa Sollievo Sofferenza Hosp, Unit Endocrinol & Diabetol, I-71013 San Giovanni Rotondo, Italy

[5] ASST G Pini CTO, Dept Rheumatol & Med Sci, Bone Dis Unit, I-20122 Milan, Italy

[6] Sapienza Univ Rome, Dept Clin Internal Anaesthesiol & Cardiovasc Sci, I-00161 Rome, Italy

[7] IRCCS, Casa Sollievo Sofferenza Hosp, Div Med Genet, I-71013 San Giovanni Rotondo, Italy

[8] Univ Padua, Dept Med, European Reference Network Rare Bone Dis ERN BOND, Clin Med 1, I-35128 Padua, Italy

[9] Natl Res Council CNR, Inst Clin Physiol IFC, I-56124 Pisa, Italy

[10] Univ Verona, Dept Med, Rheumatol Unit, I-37129 Verona, Italy

[11] FIRMO Fdn, Italian Fdn Res Bone Dis, I-50129 Florence, Italy

[12] CE Med Writing SRLS, I-56124 Pisa, Italy

来源：

JOURNAL OF BONE AND MINERAL RESEARCH | 2024年 / 40卷 / 01期

关键词：

hypophosphatasia; bone turnover markers; alkaline phosphatase; osteoporosis;

D O I：

10.1093/jbmr/zjae177

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Hypophosphatasia (HPP) is a rare disorder of the bone metabolism, characterized by genetically determined low alkaline phosphatase (ALP) activity. Low ALP may also be observed in some common causes of bone fragility, such as in osteoporosis treated with antiresorptive drugs. This study aimed to verify whether differences in bone turnover markers (BTMs) could help differentiate adult patients with HPP from those with osteoporosis undergoing antiresorptive treatment. In this multicenter study, we enrolled 23 adult patients with a diagnosis of HPP and compared them with 46 osteoporotic subjects previously treated with zoledronic acid or denosumab. BTMs such as CTX, N-terminal propeptide of type I procollagen (P1NP), total ALP, and bone ALP (bALP) were measured, and ratios between BTMs were also calculated. Considering that the control group included only females, in the primary analysis we compared their characteristics with that of the 16 female patients with HPP. Both individual BTMs (CTX and P1NP) and 4 BTM ratios (ALP/P1NP, bALP/P1NP, ALP/CTX, and bALP/CTX) showed satisfactory discriminatory power, outperforming ALP alone. P1NP, in particular, had an area under the curve (AUC) of 0.962 with a cut-off of 32 mu g/L, while as for the BTMs ratios, the ALP/P1NP ratio had an AUC of 0.964 with a cut-off of 1.114. Similar results were confirmed when including male HPP patients, when adjusting for age and sex, and finally when performing a sensitivity analysis only in patients with ALP less than or equal to 32 U/L (ie, the median of the distribution of the entire population). In cases of low ALP and bone fragility, BTM and their ratios could help distinguish HPP patients from osteoporotic individuals treated with antiresorptive drugs, aiding in accurate diagnosis and reducing the risk of inappropriate treatment. Hypophosphatasia (HPP) is a rare bone disease caused by mutations in the ALPL gene, leading to low activity of alkaline phosphatase (ALP). This enzyme deficiency affects bone mineralization, causing a wide range of symptoms, with severe cases potentially resulting in stillbirth. In contrast, milder forms can be mistaken for common bone diseases like antiresorptive-treated osteoporosis, leading to misdiagnosis and inappropriate treatments that may worsen bone fragility in HPP patients. Diagnosing HPP primarily relies on measuring plasma ALP activity, but low ALP is not specific to HPP and can occur in other conditions. Confirmatory tests, including specific biomarkers and genetic analysis, are often expensive and not widely available. Our study explores the use of bone turnover markers (BTMs) to help diagnose HPP. We found that HPP patients show distinct patterns in BTMs compared to those with antiresorptive-treated osteoporosis. These findings suggest that measuring BTMs and their ratios could help distinguish HPP from primary osteoporosis in patients with low ALP and bone fragility. This approach could lead to earlier and more accurate diagnoses, prompting further specific tests for HPP. More research is needed to confirm these findings in other conditions with low ALP activity.

引用

页码：79 / 86

页数：8