Table.

Roles of PINP in the management of metabolic bone disorders.

1. Assessment of bone formation

Mainly in the osteoporosis research setting, including drug trials.2–4

2. Assessment of bone turnover

PINP reflects bone turnover overall due to coupling of bone resorption and bone formation. Mainly used in the research setting currently.2–4

3. Assessment of osteoporosis risk i.e. stratification

Whilst a raised PINP is an independent risk factor for fracture risk, there are not enough data to confirm its role as an independent factor in fracture risk calculations when all other risk factors are included.23,24

4. Assessment of response to osteoporosis treatments – anabolic and antiresorptives

The main role is assessment and monitoring of BTM in osteoporosis treatment. A significant decrease in PINP following antiresorptive therapy and a significant increase following anabolic therapy confirms response to therapy.29,30

5. Monitoring of response to treatment

Useful for confirming adherence i.e. compliance and persistence with treatment.34

6. Monitoring for offset of treatment on cessation

On treatment cessation, an increase in PINP to baseline or greater than the premenopausal median may indicate offset of treatment effect i.e. increased bone turnover and increase in risk of fracture which may inform the need to restart bisphosphonate therapy. With denosumab therapy, a rapid rebound increases the risk of fracture (return to baseline risk) and may require restarting denosumab, or instituting bisphosphonate therapy to blunt the rapid offset before cessation.37,40

7. Monitoring of safety e.g. bone suppression and adynamic bone disease in CKD

Currently there are no data for the use of PINP to diagnose over-suppression of turnover and risk of osteonecrosis of the jaw or atypical fracture in osteoporosis therapy.

There is potential for the use of intact PINP assays to monitor bone turnover in CKD; however, data from clinical studies are lacking for this purpose.

8. Diagnosing Paget’s disease of bone

Whilst total ALP or bone ALP (if liver disease is present) measurement, together with imaging studies, is adequate for the diagnosis of Paget’s disease of bone, the increased sensitivity and specificity of PINP may be useful in diagnosing monostotic Paget’s disease.41,42

9. Monitoring of disease activity in Paget’s disease

As above, total ALP is adequate in most cases of Paget’s disease of bone to monitor therapy and detect recurrence; PINP is more sensitive and may be used as back-up or where ALP is elevated due to other causes.41–43

10. Metastatic bone disease

There is potential for the use of PINP both in detecting metastatic bone disease as well as in monitoring of treatment, especially for osteoblastic secondaries such as prostate cancer, breast cancer etc. This area requires further study.46

BTM, bone turnover markers; CKD, chronic kidney disease; ALP, alkaline phosphatase.