Impact of BMD Measurement in the Evaluation of 10 Years Absolute Risk of Fracturey

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Polska Fundacja Osteoporozy ul. Waryńskiego 6/1, 15-461 Białystok Tel/Fax: +48 (0) 85 744 54 40 Regon 050055137, NIP 542-19-76-675 e-mail: fundacja@pfo.com.pl Prezes: Prof. Janusz E. Badurski Konto bankowe: Bank Śląski SA O/Białystok 33105018231000002250469620

Impact of BMD Measurement in the Evaluation of 10 Years Absolute Risk of Fracture and Intervention Threshold in Postmenopausal Women. A Polish Perspective.

Dobrenko A., Badurski J.E., Nowak N.A., Daniluk S., Jeziernicka E.
Center of Osteoporosis and Osteoarticular Diseases, and Polish Foundation of Osteoporosis, Bialystok, Poland.

BACKGROUND

The essence of osteoporosis is decreased of bone strength being a risk of low trauma fractures. In every day practice it requires the evaluation of the individual risk of the fracture (IRF) and of the need of intervention. The assessment of IRF needs taking into account all known independent risk of fracture. Low bone mineral density (BMD) is one of them. Normal or osteopenic BMD does not decrease risk of fracture in the presence of another independent causes of fractures. BMD itself also does not discriminate persons with or without fractures. The majority of osteoporotic fractures (1,2) affects persons with BMD above T-score -2.5, which was considered as threshold of osteoporosis formerly. In Bialystok Osteoporosis Study (BOS) conducted in Poland (3,4), the average T-score of the persons who experienced fractures was -1.6 if measured at Lumbar Spine and -1.9 if in Femoral Neck. This way, wrong interpretation of the meaning of BMD can strongly underestimate need of treatment.

Several nationally oriented analyses considered treatment intervention (TI) threshold on different levels oscillating between 10% (5), 14% (6) up to 20% and 25% (7) of absolute, 10-years risk of hip fracture (AR-10), but one threshold for all ages. We are considering the possibility to involve the life-time risk into the 10-year absolute risk of fracture by the application of increased with age TI threshold. Namely, at the age 50-59 TI threshold would be as height as 10% of AR-10, at 60-69 – 15%, at 70-79 – 20%, and over 80 – 25% respectively.

THE PURPOSE OF STUDY

The estimation of frequency of occurrence IRF in particular decades of adult women’s life.
The evaluation of impact of age and hip BMD on AR-10 level.
The estimation of proportion of patients who would be treated if decision is taken on the basis of densitometric criteria (DXA T-score -2.5) only, if on AR-10 assessed only by clinical risk factors questionnaire (CRFQ), and if on combination of CRFQ and BMD DXA with every Z-score and with Z-score only below 0.0.
The estimation of proportion of patients who would require treatments when TI threshold is 14% if BMD DXA is expressed by every Z-score and if by Z-score below 0.0 only.
The estimation of proportion of patients who require treatment at proposed by us increased with age TI threshold, and impact of BMD DXA on these TI threshold.

PATIENTS AND THE METHODS

906 women from database of our center, in the mean age 64,3 years, volunteers, who completed CRFQ and passed BMD DXA of Hip in last two years. Their demographic data are in Table 1.

Table 1. The demographic data
	Mean	SD	Min	Max
Age	64,3	4,9	20,0	87,0
Height	158,8	6,5	137,5	178,0
Weight	70,4	12,2	43,0	122,0
BMI	28,3	6,2	16,6	40,8

The estimation of hip fracture risk was based on a algorithm elaborated by Kanis et co. (8). An individual relative risk (IRR) was calculated by multiplication of coefficients representing each independent risk factor (IRF). AR-10 of every examined women was calculated by multiplication of IRR and AR-10 of Swedish women population as in Table 2. Independent risk factors (IRF) of hip fracture and corresponding relative risk (RR) has been listed in Table 3:

Table 2. Individual relative risk (IRR) vs AR-10 of Swedish women population at different ages: Calculation of individual, absolute, 10-years risk of hip fracture (AR-10).
Indywidual RR	AR-10 of Swedish women population at different ages
Indywidual RR	50 years	60 years	70 years	80 years
1,0	0,6	2,4	7,9	18,0
2,0	1,1	4,8	15,1	32,0
3,0	1,7	7,0	21,7	42,9
4,0	2,3	9,3	27,7	51,6

Table 3. The CRFQ: Independent risk factors (IRF) of fractures and corresponding coefficient RR evaluated by epidemiological studies.
Questions:	RR
Q1. Previous low trauma fracture after 40	1,7
Q2. Family history of hip fracture	2,2
Q3. Secondary Osteoporosis (Rheumatoid Arthritis)	1,8
Q4. Chronic therapy with glycocorticosteroids (GS)	2,3
Q5. Smoking	1,7
Q6. Alcohol abuse	1,7
Q7. BMI<19	1,8
Q8. BMD	2.6/Z-score

To involve low bone mass as the independent fracture risk factor, we use meta-analysis by Marshall et co. (9) indicating increase of hip fracture risk of 2.6 times on every 1.0 SD below age-matched Z-score (Table 4). Hip BMD by DXA was measured using Hologic QDR4500SL. We recorded the lowest Z-score from Neck and Total Hip.

Table 4. Increase of relative risk of fracture with decrease of BMD on every Z-score –1.0.
Miejsce pomiaru	Forearm fracture	Hip fracture	Spine fracture	Any fracture
Forearm	1,7	1,8	1,7	1,4
Hip	1,4	2,6	1,8	1,6
Lumbar spine	1,5	1,6	2,3	1,0

RESULTS

Assessment of fracture risk factors

The occurrence of the fracture risk factors in every life decade in order from Q1 to Q8 by CRFQ is shown on Table 5 and Fig. 1.

Table 5. Incidence of particular, independent fracture risk factors before and at 6, 7, 8, and 9 decades of life in population of 906 women.

Age n	Q1		Q2		Q3		Q4		Q5		Q6		Q7		Q8
	Previous low trauma fracture after 40		Family history of hip fracture		Secondary Osteoporosis (Rheumatoid Arthritis)		Chronic therapy with glycocortico steroids (GS)		Smoking		Alcohol abuse		BMI<19		Z-score<0
	n	%	n	%	n	%	n	%	n	%	n	%	n	%	n	%
Below 50 (n=103)	24	23,3	29	28,2	6	5,8	4	3,9	18	17,5	0	0	8	7,8	87	84,5
50-59 (n=168)	36	21,4	32	19,0	10	6,0	4	2,4	46	27,4	0	0	2	1,2	104	61,9
60-69 (n=237)	74	31,2	26	11,0	12	5,1	1	0,4	30	12,7	4	1,7	2	0,8	82	34,6
70-79 (n=388)	122	31,4	60	15,5	3	0,8	1	0,3	84	21,6	3	0,8	5	1,3	48	12,4
above 80 (n=10)	5	50	0	0	0	0	0	0	0	0	0	0	0	0	5	50
All groups (n=906)	261	28,8	147	16,2	31	3,4	10	1,1	178	19,6	7	0,8	17	1,9	326	35,9

Fig. 1 Incidence of particular, independent fracture risk factors before and at 6, 7, 8, and 9 decades of life in population of 906 women (graph)

Previous fracture, the family history of hip fracture and smoking are the most frequent risk factors. In 6^th and 7^th decade of life also low BMD and secondary osteoporoses, mainly Rheumatoid Arthritis, participate in decrease of bone strength in population examined. The large proportion of young women with BMD below the age-matched Z-score speaks rather for lower than manufacturer’s normative populations pick bone mass of polish women then for exceedes of bone resorption and can be wrongly interpretated.

On the contrary, the size of impact of age on AR-10 in comparison to other clinical risk factors (CRFQ from Q1 to Q7), BMD excluded, is shown below:

Table 6. Comparative analysis between relative risks (RR) evaluated by CRFQ (Q1 to Q7), Absolute Risk (AR-10) including age, and AR-10 with all Z-score and Z-score only below 0.0
Age (n)	RR CRFQ Q1-Q7		AR-10 Including age		AR-10 _DXA only Z<0		AR-10 _DXA all Z score
Age (n)	mean	SD	mean	SD	mean	SD	mean	SD
<50 (n=103)	2,1	1,3	1,2	0,7	4,0	4,7	3,9	4,7
50-59 (n=168)	1,8	1,1	2,5	2,0	4,1	4,5	3,8	4,7
60-69 (n=237)	1,7	1,2	8,6	5,9	11,6	13,8	9,0	13,7
70-79 (n=388)	1,7	0,9	16,2	7,4	18,4	14,8	10,4	15,0
>80 (n=10)	1,4	0,4	21,9	4,1	35,9	21,3	32,7	24,1
Wszyscy (n=906)	1,8	0,6	10,0	0,9	18,4	14,8	10,4	9,3

Fig.2. Relative risks other than age (left yellow bars) and Absolute Risk (AR-10) including age (right green bars) evaluated without BMD.

Fig. 3 Graph summarizing differences between AR-10 evaluated without BMD, AR-10 with BMD, with any Z-score and with Z-score only below 0.0.

In comparison to AR-10 calculated without BMD, AR-10 with BMD Z-score only below 0.0 according to Marshall’s meta-analysis in all ages is higher, taking into the consideration all independent fracture risk. BMD expressed by all Z-score causes underestimation of need of treatment.

Impact of different measures of BMD on intervention threshold

The Study 1.

The Fig. 4. shows the percentage of women (n = 906 is 100%), who would be treated if decision were made on the basis of T-score -2.5 only, or on 14% AR-10 calculated by use of CRFQ only, and with and without BMD.

Figs. 4. Proportion of women who would be treated if TI threshold were equal to T-score –2.5 only, or if TI were on 14% AR-10 calculated by use of CRFQ alone, and with or without BMD.

Similarly to results showed on the Fig.4, proportion of women who would be treated if criterion were T-score –2.5 is similar ( 9,5% vs 11,7%) to that evaluated by CRFQ + BMD with any Z-score, but these are a mostly different group of women. Also as seen in Fig.4 TI threshold assessed by both, CRFQ and BMD with Z-score only below 0.0, showed real proportion of women who should be treated, if 14% of AR-10 is accepted.

The study 2:

Population of 906 women, after calculation of AR-10 by use of CRFQ, was divided into three groups according to a procedure suggested by O. Johnell (6) with 14% of AR-10 as a threshold of TI.

First group, women with AR-10 below 8%, does not need any intervention. Second group, women with AR-10 between 8% and 14% requires additional BMD measurement and then recalculation of AR-10. Third group, women with AR-10 above 14%, would qualify to treatment without any additional procedures. In order to evaluate impact of any BMD Z-score or of BMD Z-score only below 0.0 on proportion of women who cross the threshold of 14%, we measured BMD in all three group. (Fig. 5).

Fig. 5. Changes of the proportion of women who met and do not met criteria for treatment (AR-10 14%) depend on expression of BMD: with any Z-score or Z-score only below 0.0.

As expected, the inclusion of BMD into the group with risk as low as 8% did not change the qualification to treatment (100 % before and 96.6 % after hip BMD do not exceeded threshold of TI). It confirms the lack of necessity of BMD measurement in persons with low risk estimated by CRFQ. In the middle group, BMD measurement changed qualification to treatment by 9.1% (100% before and 90.1% after hip BMD do not exceeded threshold of TI). The largest changes were seen after the BMD measurement in women, who already crossed the 14% threshold assessed by CRFQ. If every Z-score would comply, then only 30.6 % patients would stay above the 14% threshold. Taking under consideration Z-score only below 0.0, 100% of that group of women confirms the need of treatment.

Suggestion of the use of Age Dependent Threshold (ADT).

Young person lives longer being burdened by any of risk factor then older one, that is the need to take into the consideration life risk of fracture. We realize, that any one TI threshold will overestimate or younger or older population. That is way we suggest to use TI threshold increased with age (ADT), namely: 10%, 15%, 20% and 25% in 6^th, 7^th, 8^th and over decades of life respectively. Analysis of consequences of such strategy and the impact of different interpretation of BMD showed Table 7.

Table 7. Suggested ADT and the impact of different applications of BMD Z-score
Intervention threshold ADT	Age n	AR-10_{without DXA}				RR-10_{DXA any Z-score}				RR-10_{DXA Z-score <0}
		Below ADT		Above ADT		Below ADT		Above ADT		Below ADT		Above ADT
		n	%	n	%	n	%	n	%	n	%	n	%
10%	Poniżej 50 n=103	103	100	0	0	95	92,2	8	7,8	95	92,2	8	7,8
10%	50 – 59 n=168	165	98,2	3	1,8	157	93,5	11	6,5	157	93,5	11	6,5
15%	60 – 69 n=237	214	90,3	23	9,7	213	89,9	24	10,1	198	83,5	39	16,5
20%	70 – 79 n=388	293	75,5	95	24,5	356	91,8	32	8,2	273	70,4	115	29,6
25%	Powyżej 85 n=10	5	50	5	50	5	50	5	50	3	30	7	70
All groups (n)		780		126		826		80		726		180
Proportion of women above ADT (who should be treated)		14%				9%				20%

Summarizing, among 906 patients analyzed, by the use of ADT:

would require treatments, if AR-10 were calculated by CRFQ only,
would be treated after inclusion of BMD with any Z-score and
would met criteria for treatment if AR-10 were calculated by CRFQ + BMD with Z-score only below 0.0.

Fig. 6. Proportions of women in each decade of life who would be treated if ADT, with and without BMD, were used

As in the previous studies, AR-10 calculated with BMD and any Z-score markedly underestimates need of treatment, particularly in 7^th and 8^th decades of life, where largest number of fractures occur. Because of 14%AR-10 as a TI threshold is mostly popularized in Europe, we compare it and ADT in regard to consequences of the use of both of them, especially on proportion of women needed treatment. As previously, the fracture risk was calculated with the use of CRFQ only, CRFQ and with BMD measurement.

Fig. 8. Comparative study of proportion of women, who would be treated if 14% TI threshold or ADT in each decade of life were used.

a) ADT calculated with CRFQ only

b) ADT calculated with BMD ( Z-score only < 0)

c) ADT calculated with BMD (all Z-score)

CONCLUSIONS

In order to properly evaluate AR-10, CRFQ + BMD with Z-score only below 0.0 should be use.
In comparison to 14% TI threshold, ADT reduces proportion of women needed intervention the stronger the older age is concern, giving younger persons better chance to be treated.
If the only CRFQ is used, assessment of AR-10 is equally possible, as shown on Fig. 5, where 25,5% of population would be treated after only CRFQ criteria vs 29,2 if CRFQ+BMD is used.

REFERENCES:

Burger H. et co.: Am J Epidemiol 2000, 9;147:871.
Wainwright S.A. et co.: J Bone Miner Res 2001, 16:S155.
Nowak N. et co.: Postepy Osteoartrologii 2003,14/1:1.
Badurski JE. et co.: Postepy Osteoartrologii 2003, 14/2:33.
Kanis J.A. et co.: Bone 2002, 31; 1:26.
Johnell O.: When is intervention worthwhile in osteoporosis. BBC5 Naantali 2005.
Richards JB et co.: A comparison of fracture risk classification systems and estimated rates of treatable osteoporosis; IOF World Congress On Osteoporosis, Toronto 2006.
Kanis J.A. et co.: Assessment of fracture risk. Osteoporosis Int 2005, 16:581-589
Marshall D.et co.: Br Med. J 1996, 312:1254.

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