Check CTX or PINP at three months to see whether an oral bisphosphonate is working

Design

Secondary analysis of a 2-year randomised trial of three oral bisphosphonates

Population

108 postmenopausal women under 85

Primary outcome

Response rate beyond least significant change; expected change

Effect

CTX 96% and PINP 94% at 3 months vs spine BMD 47% and hip BMD 24% at 2 years

Many patients prescribed oral bisphosphonates do not take them correctly, and repeat DXA is slow and noisy. This study re-analysed a randomised trial in which 108 postmenopausal women took alendronate, ibandronate or risedronate for two years, to compare bone density and bone turnover markers as monitoring tools.

The markers performed far better. CTX and PINP exceeded their least significant change at three months in 96% and 94% of women; lumbar spine and total hip BMD did so at two years in only 47% and 24%. Signal-to-noise ratios were about 9-10 for the markers against 2-4 for BMD.

The authors propose an 'expected change': the fall seen in 90% of adherent patients. CTX and PINP met that test (falls of 0.233 ng/mL and 12.1 ng/mL); BMD did not.

In practice, a baseline and three-month CTX or PINP gives an early answer on adherence and response. Standardise sample timing — CTX should be fasting and in the morning — and use the same laboratory.

• Measure CTX or PINP before starting an oral bisphosphonate and again at three months.
• A fall in CTX or PINP was seen in about 95% of adherent women.
• Most adherent women did not show a significant BMD change on repeat DXA at two years.
• Take CTX samples fasting and in the morning, in the same laboratory each time.
• Where markers do not fall, check how the tablet is being taken before changing drug.

Why it matters

It gives an answer in three months rather than two years, when a non-adherent patient may already have fractured.

Don't overread it

This tests markers as a response check, not whether marker-guided monitoring reduces fractures.

The statistics, in plain English

A higher signal-to-noise ratio means a real change stands out more clearly from measurement error. Only 24% of adherent women showed a hip BMD change beyond measurement error, so a 'no change' DXA says little about adherence.

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