Monitoring Monitoring Osteoporosis TherapyOsteoporosis Therapy

Dr Omar HusseinProfessor of Radiology

Ain Shams University

Clinical QuestionsClinical Questions

Why monitor osteoporosis therapy?

Will the results of the repeat DXA scan change your management?

If a repeat DXA scan is ordered, how do you know if the change is real?

Rationale Rationale

Many factors that are not clinically apparent could lead to a suboptimal response to therapy :

Long-term compliance and persistence with therapy is poor; only about 50 percent of patients who begin an osteoporosis drug continue therapy for at least one year.

Some patients do not maintain a sufficient intake of calcium or vitamin D to achieve the full benefit of therapy.

 

Rationale Rationale Malabsorption caused by a variety of GIT

disorders, including asymptomatic celiac disease, may impair treatment effect.

Other conditions with adverse skeletal effects, such as multiple myeloma or increased thyroid hormone levels, may be present but undetected before therapy, or may develop during therapy.

RationaleRationale

Various circumstances may affect decisions about continuing or modifying treatments◦Prognosis◦Responsiveness to treatment◦Possibility for changing to a lower-risk

intervention◦Resident satisfaction with the benefits of—or

concern about complications related to—treatment

5

BMD measurement:BMD measurement:

Raisz L. N Engl J Med 2005;353:164-171

1. Dual-Energy X-Ray Absorptiometry:

Results expressed as• T-SCORE is the number of SD the

measurement is above or below the YOUNG-NORMAL MEAN BMD.

• Z-SCORE is the number of SD the measurement is above or below the AGE-MATCHED MEAN BMD.

Sites used for measurement per WHO criteria:

• Total proximal femur• Femoral neck• Lumbar spine• 33percent(1/3rd) radius

Peripheral skeletal sites predict global # risk, however not used in WHO/FRAX criteria therefore limited value. Changes to therapy at these sites are slow.

SQ Mild SQ Severe

1

1

3

3

Lateral Vertebral Lateral Vertebral Assessment (using DXA):Assessment (using DXA):

Qualitative and quantitative

Semi-quantitative grading (Genant et al 1993)

Normal

Anterior Middle Mild fracture

Middle Moderate fracture

MiddleSevere fracture

Anterior

Anterior

Posterior

Posterior

Posterior

(Source: Genant HK et al, JBMR 1993; 8:1137-1148)

Grade

0

1 (~20-25%)

2 (~25-40%)

3 (~40%)

Using BMD to Monitor Therapy in Using BMD to Monitor Therapy in Treating Osteoporosis: Treating Osteoporosis:

Lewiecki  EM, Watts  NB.  Assessing response to osteoporosis therapy.  Osteoporos Int.   2008;19(10):1363–1368.

What Is Precision Error?What Is Precision Error?PE reflects the reproducibility of a

measurement when performed under identical circumstances in the setting of no real biologic change.

Factors that affect precision for Factors that affect precision for DXA ScansDXA Scans

Equipment Number of MeasurementsOperator Dependent Variables

How To Calculate Precision?How To Calculate Precision?Scan

◦15 individuals 3 times

◦30 individuals 2 times

Use patients representative of your typical patient population

Reposition between each scanFrom these measurements radiologist is

able to calculate precision for specific center

Bonnick SL, et al. J Clin Densit 2001; 4:105

Precision is Important because it Precision is Important because it allows Least Significant Change allows Least Significant Change

(LSC) to be calculated(LSC) to be calculated

What is Least Significant What is Least Significant Change (LSC)?Change (LSC)?

Precision error at your center

Desired confidence level (95%)

LSC = 2.8 x precision error

Only changes exceeding 2.8 times the precision error can be considered clinically significant within the 95% confidence interval.

Spine BMD with antiresorptive agents Dotted line indicates LSC at 1 and 2 years

Deal, Current Rheumatology Reports, 2002 - adapted from McClung

Hip BMD with antiresorptive agents- Dotted line indicates LSC at 3 years

Deal, Current Rheumatology Reports, 2002 - adapted from McClung

Confounding Variables that affect Confounding Variables that affect

DXA ScanningDXA Scanning

Aortic calcifications OsteophytesCompression fracturesSkeletal diseases ie. Pagets disease

Current Current recommendations for recommendations for

monitoring osteoporosis monitoring osteoporosis therapytherapy

Bone MarkersBone Markers

Bone markersBone markers

Diagnosis of osteoporosis is not based on evaluation of bone markers, and bone mineral density (BMD) assessment is still the criterion standard for evaluation and diagnosis. 

A study done by Kumar et al, 2008 showed that osteocalcin showed a significant correlation with BMD and other bone markers did not correlate with the underlying BMD. Even though changes in bone metabolism cannot be identified by the determination of a single bone marker, improved biochemical measurement may provide early information about osteoporosis. Because of the variability of bone turnover markers, BMD determination still remains the best modality currently available for evaluation of osteoporosis

Bone Markers and Bone Density, Endocr Pract  2008;14(No. 9)

Several studies confirmed that short-term reductions in bone turnover were associated with a reduction in vertebral and/or non-vertebral fracture risk in women.

Clin Biochem Rev. 2006 August; 27(3): 123–138.Biochemical Markers of Bone Turnover Part II: Clinical Applications in the Management of Osteoporosis

There are data suggesting that biochemical markers of bone turnover are useful tools to evaluate therapeutic effects after a relatively short period of time, and that serial measurements of bone markers may help to decide whether or not a patient responds to a specific antiresorptive treatment. 

As bone turnover markers, in particular indices of bone resorption, decrease rapidly after initiation of treatment within three to six months, they might represent useful surrogate markers for monitoring patient compliance. Only few data, however, are available to support this theoretical approach. 

Clin Biochem Rev. 2006 August; 27(3): 123–138.Biochemical Markers of Bone

Turnover Part II: Clinical Applications in the Management of Osteoporosis

To concludeTo conclude

Precision and LSC must be considered to obtain reliable results from repeat DXA scans.

Changes in BMD are more precisely measured at sites of trabecular bone, ie. the spine

Increase in BMD is only part of the fracture risk reduction story.

To ConcludeTo Conclude

A statistically significant BMD loss may lead to further evaluation and possibly a change in treatment.

The strategy of monitoring therapy with BMD testing is supported by the medical evidence, consistent with clinical practice guidelines, and makes good clinical sense.