As Mary S. (71) puts down her heavy shopping bag, she suddenly feels a sharp pain in her forearm. Her general practitioner, whom she visits the next day, immediately refers her to radiology. The x-ray confirms the suspected diagnosis of a fractured radius. But that is not all. Mary also appears to suffer from osteoporosis, as confirmed by a subsequent bone density test. This bone disease reduces bone density so that only a small amount of force is needed to cause fractures. In many cases, there are no symptoms and the fractures are only discovered later. Some of Mary’s vertebrae show changes in shape typical of osteoporosis – the result of undetected fractures. * However, once osteoporosis is diagnosed, treatment and disease monitoring can be started quickly to aid in the prevention of further damage.
Osteoporosis – a bone disease with endocrine causes
Osteoporosis is a bone disease that occurs worldwide and leads to bone loss and reduced bone strength. Osteoporosis affects about one third of women and one fifth of men. Post-menopausal women, like Mary, are particularly at risk of osteoporosis because the production of the female sex hormone oestrogen, which protects against bone loss, slows down during menopause. Calcium and vitamin D deficiencies, which can also occur with age, also contribute to the loss of bone mass. The first sign of osteoporosis is often a fracture, as the bone loss itself does not cause any symptoms. Diagnosis is primarily made by bone density test, followed by therapeutic measures such as anti-resorptive or anabolic medication in addition to intake of calcium and vitamin D as well as bone-fortifying exercise. A consensus paper from key experts in the field of bone metabolism recommends the use of bone turnover markers for monitoring anti-resorptive drugs and prediction of fracture risk in post-menopausal osteoporosis since 2011 1.
Bone turnover markers (BTMs) in diagnostics
In healthy individuals, bone remodelling, a lifelong process consisting of bone resorption and bone formation, is in balance and results in a constant bone mass. The process is tightly regulated by systemic hormones and local mediators such as parathyroid hormone, vitamin D, cytokines and growth factors. Bone turnover markers allow reliable assessment of bone turnover as they are produced during bone remodelling and are released from bone.
A distinction is made between formation markers such as PINP (procollagen type I N-propeptide), osteocalcin and BALP (bone-specific alkaline phosphatase), which reflect different aspects of bone formation and osteoblast function, and resorption markers, e.g. β-CTX-I (β-isomerised C-terminal telopeptides of type I collagen), NTX-I (N-terminal telopeptides of type I collagen) and TRACP5b (tartrate-resistant acid phosphatase isoform 5b), which are associated with the degradation of the mineralised bone matrix and osteoclast function 2. BTMs can also be used in the diagnostic assessment of other endocrine bone diseases:
- Paget’s disease (the second most common metabolic bone disease after osteoporosis; a chronic condition associated with dense but fragile bones due to excessive bone resorption and unstructured bone formation)
- Hypophosphatasia (a rare genetic disorder resulting in defective mineralisation of the teeth and bones)
- Osteomalacia (associated with particularly soft bones caused by a bone mineralisation disorder, most commonly due to vitamin D deficiency)
Bones in calcium metabolism – vitamin D deficiency and CKD-MBD
Bones store calcium, which means that they are not only essential for stabilising the body, but they also serve as an important calcium reservoir in the homeostasis of this mineral. The active uptake of calcium via the intestinal epithelial cells is regulated by calcitriol (1,25-dihydroxy vitamin D), which is produced in a reaction chain from 7-dehydrocholesterol via intermediates, e.g. 25-(OH) vitamin D. The first step takes place in the skin with the help of UV radiation. The final step, conversion into the biologically active hormone primarily in the kidneys, is regulated by parathyroid hormone (PTH) from the parathyroid glands. If there is not enough calcium to absorb, PTH stimulates bone resorption, which releases calcium into the blood. If the blood calcium level is too high, the thyroid hormone calcitonin is released in higher amounts to reduce the calcium level.
If this complex process is out of balance, this can lead to more than just vitamin D deficiency and the negative consequences for bone stability (e.g. bone loss, osteomalacia). Patients with chronic kidney disease may also develop CKD-MBD (chronic kidney disease – mineral and bone disorder), a systemic disease that affects about five to ten percent of the world’s population. Impaired renal function causes irregularities in mineral metabolism affecting levels of calcium, phosphorus, PTH and vitamin D. This not only changes bone structure but also leads to calcification of the blood vessels, resulting in an increased fracture and cardiovascular risk. The BTMs currently recommended for the management of osteoporosis, β-CTX-I and total PINP, are not suitable in the setting of renal failure. A position paper recently published recommends BALP and TRACP5b as reference markers in CKD-associated osteoporosis as they are not affected by kidney function 3.
These endocrine bone diseases can be identified and monitored using high-quality diagnostic test systems. EUROIMMUN and IDS offer a comprehensive portfolio of fully automated chemiluminescence assays, which includes all biomarkers recommended for osteoporosis management according to the latest findings 3 and allows the quantification of all BTMs independently of renal function 4–6:
Immunoassays for bone formation markers
- IDS Intact PINP
- IDS N-MID Osteocalcin
- IDS Ostase BAP
Immunoassays for bone resorption markers
- IDS Beta CrossLaps (CTX-I)
- IDS TRAcP 5b (BoneTRAP)
Immunoassays for bone and calcium metabolism
- IDS 25 VitDS
- IDS 1,25 VitDXp
- IDS 1,25 Dihydroxy Vitamin D
- IDS Intact PTH
The assays can be processed conveniently due to walk-away automation, which also allows continuous loading and unloading of samples and reagents, while providing rapid results.
EUROIMMUN and IDS bring reliability and efficiency to the management of bone diseases and calcium metabolism on one platform.
Mary is well on track with her osteoporosis treatment. Not only has she made lifestyle changes in consultation with her GP and her endocrinologist, but she is also on anti-resorptive drug therapy, which is proving to be successful, as confirmed by laboratory tests to monitor her bone marker levels.
Curious? Discover our panels and parameters for endocrinology and find out more about diagnostics in this field. If you are interested in endocrine hypertension, read the blog article on this topic.
1. Vasikaran S, et al. International Osteoporosis Foundation and International Federation of Clinical Chemistry and Laboratory Medicine position on bone marker standards in osteoporosis. Clin Chem Lab Med 49(8): 1271 – 1274 (2011).
2. Lombardi G, et al. Guidelines for the correct use of the nomenclature of biochemical indices of bone status: a position statement of the Joint IOF Working Group and IFCC Committee on Bone Metabolism. Clin Chem Lab Med 63(4): 704 – 711 (2024).
3. Bhattoa, HP et al. Update on the role of bone turnover markers in the diagnosis and management of osteoporosis: a consensus paper from The European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO), International Osteoporosis Foundation (IOF), and International Federation of Clinical Chemistry and Laboratory Medicine (IFCC). Osteoporos Int (2025). (published online)
4. Tridimas A, et al. Assessing bone formation in patients with chronic kidney disease using procollagen type I N-terminal propeptide (PINP): The choice of assay makes a difference. Ann Clin Biochem 58(5): 528 – 536 (2021).
5. Cavalier E, et al. Analytical evaluation of the Nittobo Medical tartrate resistant acid phosphatase isoform 5b (TRACP-5b) EIA and comparison with IDS iSYS in different clinically defined populations. Clin Chem Lab Med 60(3): 394 – 400 (2021).
6. Vasikaran S, et al. Practical Considerations for the Clinical Application of Bone Turnover Markers in Osteoporosis. Calcif Tissue Int 112(2): 148 – 157 (2023).
* This is a fictional example case.