Bone metabolism subgroups identified as hip fracture patients via clustering



The aim of the study was to describe the bone metabolism status that underlies a hip fracture.


Estimated glomerular filtration rate (e-GFR), calcium (Ca), phosphorus (P), total (ALP) and bone specific alkaline phosphatase (b-ALP), intact parathyroid hormone (i-PTH), 25-hydroxy-vitamin D (25OHD), total procollagen type I amino-terminal propeptide (PINP), and N-terminal peptide of collagen I (NTx), measured at admission in 272 hip fracture patients, were ex post analyzed by K-means clustering and principal component analysis and were evaluated by a clinician.


Four components, mainly consisting of b-ALP, PINP, ALP, and NTx; e-GFR and P; i-PTH and 25OHD; and Ca explained about 70% of the variability. A total of 184 patients clustered around a centroid (A) with low 25OHD (13.2 ng/ml), well-preserved kidney function (e-GFR=67.19 ml/min/1.73m2), normal Ca, P, i-PTH and bone markers, with the exception of slightly increased NTx (24.82nMBCE). Cluster B (n=70) had increased i-PTH (93.38 pg/ml), moderately decreased e-GFR, very low 25OHD (8.68 ng/dl), and high bone turnover (b-ALP 28.46 U/L, PINP 69.87 ng/ml, NTx 31.3nMBCE). Cluster C (n=17) also had hyperparathyroidism (80.35 pg/ml) and hypovitaminosis D (9.15 ng/ml), low e-GFR(48.89 ml/min/1.73m2), and notably high ALP (173 U/L) and bone markers (b-ALP 44.64 U/L, PINP 186.98 ng/ml, NTx 38.28nMBCE). According to the clinician, 62 cases clearly had secondary hyperparathyroidism.


Based on serum measurements, the dominant patterns of bone metabolism were normal bone turnover with high normal NTx, and secondary hyperparathyroidism related to chronic kidney disease and hypovitaminosis D. The bone formation markers, e-GFR, NTx, and P composed the most important factors.

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Data availability

Available after request.


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Special acknowledgments go to Andreas Morakis, Konstantinos Sarantos, Konstantinos Antonis, Konstantinos Skagias, Panagiota Giannikou, and Ioannis Giannakopoulos who recruited the patients and collected the samples. Software and formal analysis were kindly performed by Kleanthis Kleanthous, Analyst, and IT Architect. Special thanks to Maria Ragoussi and Maria Tsipra for handling the samples and performing the laboratory measurements.

Code availability

The open source R platform version 3.6.3 along with various open source R libraries for statistics and graphs (e.g., factoextra, cluster, ggplot2).

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Correspondence to Evangelia Papakitsou.

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Approval was obtained from the Scientific Council of KAT hospital (20/ 12-10-2004). The procedures used in this study adhere to the tenets of the Declaration of Helsinki. Informed consent was obtained from all individual participants or the supporter in case of dementia included in the study. Information is anonymized and the article does not include images that may identify any participant.

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The authors declare no competing interests.

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Papakitsou, E., Paspati, I., Rizou, S. et al. Bone metabolism subgroups identified as hip fracture patients via clustering. Hormones (2021).

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  • Chronic kidney disease
  • Clustering
  • bone markers
  • Alkaline phosphatase
  • Hyperparathyroidism
  • 25hydroxyD