Evaluation of Patients With a Recent Clinical Fracture and Osteoporosis, a Multidisciplinary Approach

Bianca Dumitrescu; Svenjhalmar van Helden; Rene ten Broeke; Arie Nieuwenhuijzen-Kruseman; Caroline Wyers; Gabriela Udrea; Sjef van der Linden; Piet Geusens

Disclosures

BMC Musculoskelet Disord

Abstract and Background

Abstract

The aetiology of osteoporotic fractures is multifactorial, but little is known about the way to evaluate patients with a recent clinical fracture for the presence of secondary osteoporosis.

The purpose of this study was to determine the prevalence of contributors to secondary osteoporosis in patients presenting with a clinical vertebral or non-vertebral fracture. Identifying and correcting these contributors will enhance treatment effect aimed at reducing the risk of subsequent fractures.

In a multidisciplinary approach, including evaluation of bone and fall-related risk factors, 100 consecutive women (n = 73) and men (n = 27) older than 50 years presenting with a clinical vertebral or non-vertebral fracture and having osteoporosis (T-score ≤-2.5) were further evaluated clinically and by laboratory testing for the presence of contributors to secondary osteoporosis.

In 27 patients, 34 contributors were previously known, in 50 patients 52 new contributors were diagnosed (mainly vitamin D deficiency in 42) and 14 needed further exploration because of laboratory abnormalities (mainly abnormal thyroid stimulating hormone in 9). The 57 patients with contributors were older (71 vs. 64 yrs, p < 0.01), had more vertebral deformities (67% vs. 44%, p < 0.05) and a higher calculated absolute 10-year risk for major (16.5 vs. 9.9%, p < 0.01) and for hip fracture (6.9 vs. 2.4%, p < 0.01) than patients without contributors. The presence of contributors was similar between women and men and between patients with fractures associated with a low or high-energy trauma.

We conclude that more than one in two patients presenting with a clinical vertebral or non-vertebral fracture and BMD-osteoporosis have secondary contributors to osteoporosis, most of which were correctable. Identifying and correcting these associated disorders will enhance treatment effect aimed at reducing the risk of subsequent fractures in patients older than 50 years.

Background

Clinical vertebral and non-vertebral fractures are the most frequent fractures in patients presenting to the emergency ward of the hospital with a fracture.^[1] After such fracture, patients are at increased risk for subsequent fracture and guidelines on osteoporosis advocate to evaluate patients presenting with a fracture in order to consider treament to reduce the risk of subsequent fractures.^[2]

One aspect of care identified within the management of fracture patients is the existence of contributors to secondary causes of bone loss.^[3] Effective therapy requires that these contributors be recognised and when present managed appropriately.^[3,4] If these conditions, however, are not recognized, treatment may be suboptimal or ineffective.^[5,6]

Apart from bone mineral density (BMD)-osteoporosis (T-score less than or equal to -2.5)^[4,7,8] many risk factors are related to fracture risk, independently of BMD, such as clinical risk factors,^[9] fall risks,^[10] prevalent morphometric vertebral fractures (MVF)^[11] and secondary osteoporosis.^[12] There is increasing evidence that secondary osteoporosis is more prevalent than initially thought, not only in males, but also in females,^[13] but the true prevalence of contributors to secondary osteoporosis is unknown and no consensus regarding its evaluation is available.^[14]

Published data from referral centres for evaluation of osteoporosis indicate that 32 to 37% of women with low BMD have a history of other diseases or medications known to contribute to osteoporosis.^[3,15] From 20% up to 64% of patients had previously unknown secondary causes of osteoporosis that were only identified by laboratory testing.^[5] In a study of patients with a clinical fracture, a high prevalence of contributors to secondary osteoporosis (77%) was reported, but the study included only a limited number of patients with measured low BMD.^[16] In a study of patients with a hip fracture, 80% had secondary causes of bone loss, mainly related to disturbed calcium and vitamin D homeostasis.^[6] To date, we lack studies on the prevalence of contributors to secondary osteoporosis in other fracture populations.

The purpose of this study was to determine the prevalence of contributors to secondary osteoporosis, in the context of other bone- and fall-related fracture risks in patients presenting with a clinical vertebral or non-vertebral fracture and with a low BMD. Identifying and correcting contributors will enhance treatment effect aimed at reducing the risk of subsequent fractures.

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Cite this: Evaluation of Patients With a Recent Clinical Fracture and Osteoporosis, a Multidisciplinary Approach - Medscape - Aug 05, 2008.

Abstract and Background
Methods
Results
Discussion
Conclusion
References

Characteristics of the Patient Population (N = 100)
Variable Median±SD	All patients	Women	Men	Fragility fracture	High energy trauma	With contributors	Without contributors
Number	100	73	27	80	20	57	43
Women/men (n)	73/27	na	na	66/14	7/13**	40/17	33/10***
Caucasian ethnicity (n)	97	94	27	79	18	55	42
Age (years)	68 ± 10	70 ± 9	62 ± 8*	69,1 ± 9	63.3 ± 9**	71 ± 10	64 ± 7***
Weight (kg)	66 ± 13	63 ± 13	73 ± 11*	65,4 ± 14	68.8 ± 11	64 ± 14	69 ± 11
Spine T-score	-2.88 ± .91	-2.94 ± 0.79	-2.73 ± 1.17	-2.9 ± 0.92	-2.8 ± 0.83	-2.85 ± 0.97	-2.93 ± 0.82
Hip T-score	-1.92 ± 0.9	-2.13 ± 0.92	-1.37 ± 0.70*	-2 ± 0.87	-1.6 ± 1.09	-2.1 ± 1.00	-0.66 ± 0.63***
Hip Z-score	-1.92 ± 0.8	-0.57 ± 0.85	-0.89 ± 0.73	-0.62 ± 0.85	-0.83 ± 0.72	-0.66 ± 0.97	-0.66 ± 0.63
BMD spine(g/sq cm)	0.772± 0.100	0.756 ± 0.085	0.810 ± 0.130*	0.765 ± 0.103	0.795 ± 0.094	0.776 ± 0.109	0.766 ± 0.091
BMD hip(g/sq cm)	0.718± 0.395	0.676 ± 0.115	0.825 ± 0.107*	0.700 ± 0.116	0.779 ± 0.160**	0.695 ± 0.143	0.749 ± 0.106
Calcium intake(mg/day)	852 ± 432	828 ± 448	915 ± 389	851 ± 467	854 ± 266	744 ± 343	993 ± 497***
Serum 25OH vitamin D (nmol/L)	66 ± 53	67 ± 60	63 ± 28	63 ± 57	75 ± 30	42	0
Creatinine clearance (ml/min)	67 ± 23	62 ± 20	65 ± 23	65 ± 23	74 ± 26	45 ± 18	82 ± 24***
Fracture after fall from standing height (n)	80	66	14	na	na	45	35
N of contributors (n)	86	62	24	70	16	na	na
N with contributors (n)	57	40	17	45	12	na	na
N with bone-related fracture risks	54	42	12	44	10	33	21
N with fall-related fracture risks	79	57	22	65	14	46	33
Time Go Up and Go (min)	8.6 ± 7.9	8.4 ± 8.0	8.9 ± 8.0	8.2 ± 8.0	9.8±8.0	8.1±8.6	9.2±7.1
N with MVD <0.80 (n/n measured)	53/93	35/66	18/27	42/73	11/20	36/54	17/39***
N with MVD <0.75	29	22	7	24	11	19	10

*p < 0.05 women vs. men, ** p < 0.05 between fragility fracture and high-energy trauma, *** p < 0.05 between group with and without contributor, Na: not applicable

Characteristics of the Patient Population (N = 100)
Variable Median±SD	All patients	Women	Men	Fragility fracture	High energy trauma	With contributors	Without contributors
Number	100	73	27	80	20	57	43
Women/men (n)	73/27	na	na	66/14	7/13**	40/17	33/10***
Caucasian ethnicity (n)	97	94	27	79	18	55	42
Age (years)	68 ± 10	70 ± 9	62 ± 8*	69,1 ± 9	63.3 ± 9**	71 ± 10	64 ± 7***
Weight (kg)	66 ± 13	63 ± 13	73 ± 11*	65,4 ± 14	68.8 ± 11	64 ± 14	69 ± 11
Spine T-score	-2.88 ± .91	-2.94 ± 0.79	-2.73 ± 1.17	-2.9 ± 0.92	-2.8 ± 0.83	-2.85 ± 0.97	-2.93 ± 0.82
Hip T-score	-1.92 ± 0.9	-2.13 ± 0.92	-1.37 ± 0.70*	-2 ± 0.87	-1.6 ± 1.09	-2.1 ± 1.00	-0.66 ± 0.63***
Hip Z-score	-1.92 ± 0.8	-0.57 ± 0.85	-0.89 ± 0.73	-0.62 ± 0.85	-0.83 ± 0.72	-0.66 ± 0.97	-0.66 ± 0.63
BMD spine(g/sq cm)	0.772± 0.100	0.756 ± 0.085	0.810 ± 0.130*	0.765 ± 0.103	0.795 ± 0.094	0.776 ± 0.109	0.766 ± 0.091
BMD hip(g/sq cm)	0.718± 0.395	0.676 ± 0.115	0.825 ± 0.107*	0.700 ± 0.116	0.779 ± 0.160**	0.695 ± 0.143	0.749 ± 0.106
Calcium intake(mg/day)	852 ± 432	828 ± 448	915 ± 389	851 ± 467	854 ± 266	744 ± 343	993 ± 497***
Serum 25OH vitamin D (nmol/L)	66 ± 53	67 ± 60	63 ± 28	63 ± 57	75 ± 30	42	0
Creatinine clearance (ml/min)	67 ± 23	62 ± 20	65 ± 23	65 ± 23	74 ± 26	45 ± 18	82 ± 24***
Fracture after fall from standing height (n)	80	66	14	na	na	45	35
N of contributors (n)	86	62	24	70	16	na	na
N with contributors (n)	57	40	17	45	12	na	na
N with bone-related fracture risks	54	42	12	44	10	33	21
N with fall-related fracture risks	79	57	22	65	14	46	33
Time Go Up and Go (min)	8.6 ± 7.9	8.4 ± 8.0	8.9 ± 8.0	8.2 ± 8.0	9.8±8.0	8.1±8.6	9.2±7.1
N with MVD <0.80 (n/n measured)	53/93	35/66	18/27	42/73	11/20	36/54	17/39***
N with MVD <0.75	29	22	7	24	11	19	10

*p < 0.05 women vs. men, ** p < 0.05 between fragility fracture and high-energy trauma, *** p < 0.05 between group with and without contributor, Na: not applicable

Contributors to Secondary Osteoporosis Identified in Men and Women >50 Years With a Recent Clinical Fracture (N = 100)
Contributors	Total	Known	Newly diagnosed	Fragility Fracture (N = 80)	High-energy trauma (N = 20)
Endocrine disorders
Serum 25-OHD₃ s ≤50 nmol/l	42	0	42	37	5
Hyperparathyroidism secondary to low calcium intake	2	0	2	1	1
Hyperthyroidism	3	3	0	3	0
Hypogonadism (in men)	1	1	0	0	1
Anorexia nervosa (in women)	2	2	0	2	0
Diabetes mellitus	5	5	0	4	1
Gastrointestinal disorders
Lactose intolerance	1	0	1	0	1
Connective tissue disorders
Rheumatoid arthritis	2	2	0	1	1
Giant-cell arteritis	1	1	0	1	0
Renal disorders
Renal insufficiency without secondary hyperparathyroidism	11	5	6	7	4
Renal insufficiency with secondary hyperparathyroidism	3	3	0	3	0
Miscellaneous
Severe immobility	3	3	0	3	0
Pulmonary diseases	5	5	0	4	1
Medication and life style
Exogenous hyperthyroidism	1	0	1	1	0
Alcohol abuse	4	4	0	2	2
Total number of contributors (N = 86)	86	34	52	69	17
Total number of patients with contributors to osteoporosis (N = 57)	57	27	50	45	12

Contributors to Secondary Osteoporosis Identified in Men and Women >50 Years With a Recent Clinical Fracture (N = 100)
Contributors	Total	Known	Newly diagnosed	Fragility Fracture (N = 80)	High-energy trauma (N = 20)
Endocrine disorders
Serum 25-OHD₃ s ≤50 nmol/l	42	0	42	37	5
Hyperparathyroidism secondary to low calcium intake	2	0	2	1	1
Hyperthyroidism	3	3	0	3	0
Hypogonadism (in men)	1	1	0	0	1
Anorexia nervosa (in women)	2	2	0	2	0
Diabetes mellitus	5	5	0	4	1
Gastrointestinal disorders
Lactose intolerance	1	0	1	0	1
Connective tissue disorders
Rheumatoid arthritis	2	2	0	1	1
Giant-cell arteritis	1	1	0	1	0
Renal disorders
Renal insufficiency without secondary hyperparathyroidism	11	5	6	7	4
Renal insufficiency with secondary hyperparathyroidism	3	3	0	3	0
Miscellaneous
Severe immobility	3	3	0	3	0
Pulmonary diseases	5	5	0	4	1
Medication and life style
Exogenous hyperthyroidism	1	0	1	1	0
Alcohol abuse	4	4	0	2	2
Total number of contributors (N = 86)	86	34	52	69	17
Total number of patients with contributors to osteoporosis (N = 57)	57	27	50	45	12

Laboratory Abnormalities That Required Further Exploration in Men and Women More Than 50 Years of Age With a Recent Clinical Fracture (N = 100)
Laboratory abnormality	Total
Exogenous hypervitaminosis D (>220 nmol/l)	1
Hypercalciuria in 24 hours urine	3
TSH 0.4-3.5 mU/L	13
- >3.5 mU/L	10
- treated hypothyroidism	9
-TSH <0.4 mU/L	1
-TSH >3.5 mU/L	3
- treated hyperthyroidism	3
-TSH >3.5 mU/L	1
-TSH <0.4 mU/L	2
Serum testosterone in men <12 nmol/L (one measurement)	1
Total number of patients	14

Clinical Risks for Fractures Recorded in Patients With a Recent Clinical Fracture According to the Dutch Guidelines
CLINICAL RISKS OF FRACTURE	Total	Women	Men	Fragility fracture	High trauma	Contributors	No contributors
Numbers of patients	100	73	27	80	20	57	43
BONE RELATED RISK FACTORS	54	42	12	44	10	33	21
History of clinical fracture after 50 years	31	23	8	25	6	19	12
History of clinical vertebral fracture	2	1	0	1	0	1	0
Mother with fracture	12	9	3	10	2	8	4
Low body weight (<60 kg)	23	20	3	18	5	15	8
Severe immobility	3	3	0	3	0	3	0
Glucocorticosteroids user	0	0	0	0	0	0	0
FALL RELATED RISK FACTORS	79	57	22	65	14	46	33
Mobility: Time Get up and Go test	24	21	3	20	4	12	12
Previous falls: 2 or more falls in the previous year	27	22	5	23	4	15	12
Medication use (benzodiazepines, antiepileptics)	16	14	2	14	2	13	3
Low activities of daily living	49	38	11	43	16*	34**	15
Osteoarthritis	48	40	8	44	4*	25	23
Snellen score-visual acuity less than 0.4	16	8	8	14	2	13	3
Urinary incontinence	19	17	2	19	0	13	6

*p < 0.05 between fragility fracture and high-energy traum fracture, **p < 0.05 between groups with and without contributors

Characteristics of the Patient Population (N = 100)
Variable Median±SD	All patients	Women	Men	Fragility fracture	High energy trauma	With contributors	Without contributors
Number	100	73	27	80	20	57	43
Women/men (n)	73/27	na	na	66/14	7/13**	40/17	33/10***
Caucasian ethnicity (n)	97	94	27	79	18	55	42
Age (years)	68 ± 10	70 ± 9	62 ± 8*	69,1 ± 9	63.3 ± 9**	71 ± 10	64 ± 7***
Weight (kg)	66 ± 13	63 ± 13	73 ± 11*	65,4 ± 14	68.8 ± 11	64 ± 14	69 ± 11
Spine T-score	-2.88 ± .91	-2.94 ± 0.79	-2.73 ± 1.17	-2.9 ± 0.92	-2.8 ± 0.83	-2.85 ± 0.97	-2.93 ± 0.82
Hip T-score	-1.92 ± 0.9	-2.13 ± 0.92	-1.37 ± 0.70*	-2 ± 0.87	-1.6 ± 1.09	-2.1 ± 1.00	-0.66 ± 0.63***
Hip Z-score	-1.92 ± 0.8	-0.57 ± 0.85	-0.89 ± 0.73	-0.62 ± 0.85	-0.83 ± 0.72	-0.66 ± 0.97	-0.66 ± 0.63
BMD spine(g/sq cm)	0.772± 0.100	0.756 ± 0.085	0.810 ± 0.130*	0.765 ± 0.103	0.795 ± 0.094	0.776 ± 0.109	0.766 ± 0.091
BMD hip(g/sq cm)	0.718± 0.395	0.676 ± 0.115	0.825 ± 0.107*	0.700 ± 0.116	0.779 ± 0.160**	0.695 ± 0.143	0.749 ± 0.106
Calcium intake(mg/day)	852 ± 432	828 ± 448	915 ± 389	851 ± 467	854 ± 266	744 ± 343	993 ± 497***
Serum 25OH vitamin D (nmol/L)	66 ± 53	67 ± 60	63 ± 28	63 ± 57	75 ± 30	42	0
Creatinine clearance (ml/min)	67 ± 23	62 ± 20	65 ± 23	65 ± 23	74 ± 26	45 ± 18	82 ± 24***
Fracture after fall from standing height (n)	80	66	14	na	na	45	35
N of contributors (n)	86	62	24	70	16	na	na
N with contributors (n)	57	40	17	45	12	na	na
N with bone-related fracture risks	54	42	12	44	10	33	21
N with fall-related fracture risks	79	57	22	65	14	46	33
Time Go Up and Go (min)	8.6 ± 7.9	8.4 ± 8.0	8.9 ± 8.0	8.2 ± 8.0	9.8±8.0	8.1±8.6	9.2±7.1
N with MVD <0.80 (n/n measured)	53/93	35/66	18/27	42/73	11/20	36/54	17/39***
N with MVD <0.75	29	22	7	24	11	19	10

*p < 0.05 women vs. men, ** p < 0.05 between fragility fracture and high-energy trauma, *** p < 0.05 between group with and without contributor, Na: not applicable

Clinical Risks for Fractures Recorded in Patients With a Recent Clinical Fracture According to the Dutch Guidelines
CLINICAL RISKS OF FRACTURE	Total	Women	Men	Fragility fracture	High trauma	Contributors	No contributors
Numbers of patients	100	73	27	80	20	57	43
BONE RELATED RISK FACTORS	54	42	12	44	10	33	21
History of clinical fracture after 50 years	31	23	8	25	6	19	12
History of clinical vertebral fracture	2	1	0	1	0	1	0
Mother with fracture	12	9	3	10	2	8	4
Low body weight (<60 kg)	23	20	3	18	5	15	8
Severe immobility	3	3	0	3	0	3	0
Glucocorticosteroids user	0	0	0	0	0	0	0
FALL RELATED RISK FACTORS	79	57	22	65	14	46	33
Mobility: Time Get up and Go test	24	21	3	20	4	12	12
Previous falls: 2 or more falls in the previous year	27	22	5	23	4	15	12
Medication use (benzodiazepines, antiepileptics)	16	14	2	14	2	13	3
Low activities of daily living	49	38	11	43	16*	34**	15
Osteoarthritis	48	40	8	44	4*	25	23
Snellen score-visual acuity less than 0.4	16	8	8	14	2	13	3
Urinary incontinence	19	17	2	19	0	13	6

*p < 0.05 between fragility fracture and high-energy traum fracture, **p < 0.05 between groups with and without contributors

Characteristics of the Patient Population (N = 100)
Variable Median±SD	All patients	Women	Men	Fragility fracture	High energy trauma	With contributors	Without contributors
Number	100	73	27	80	20	57	43
Women/men (n)	73/27	na	na	66/14	7/13**	40/17	33/10***
Caucasian ethnicity (n)	97	94	27	79	18	55	42
Age (years)	68 ± 10	70 ± 9	62 ± 8*	69,1 ± 9	63.3 ± 9**	71 ± 10	64 ± 7***
Weight (kg)	66 ± 13	63 ± 13	73 ± 11*	65,4 ± 14	68.8 ± 11	64 ± 14	69 ± 11
Spine T-score	-2.88 ± .91	-2.94 ± 0.79	-2.73 ± 1.17	-2.9 ± 0.92	-2.8 ± 0.83	-2.85 ± 0.97	-2.93 ± 0.82
Hip T-score	-1.92 ± 0.9	-2.13 ± 0.92	-1.37 ± 0.70*	-2 ± 0.87	-1.6 ± 1.09	-2.1 ± 1.00	-0.66 ± 0.63***
Hip Z-score	-1.92 ± 0.8	-0.57 ± 0.85	-0.89 ± 0.73	-0.62 ± 0.85	-0.83 ± 0.72	-0.66 ± 0.97	-0.66 ± 0.63
BMD spine(g/sq cm)	0.772± 0.100	0.756 ± 0.085	0.810 ± 0.130*	0.765 ± 0.103	0.795 ± 0.094	0.776 ± 0.109	0.766 ± 0.091
BMD hip(g/sq cm)	0.718± 0.395	0.676 ± 0.115	0.825 ± 0.107*	0.700 ± 0.116	0.779 ± 0.160**	0.695 ± 0.143	0.749 ± 0.106
Calcium intake(mg/day)	852 ± 432	828 ± 448	915 ± 389	851 ± 467	854 ± 266	744 ± 343	993 ± 497***
Serum 25OH vitamin D (nmol/L)	66 ± 53	67 ± 60	63 ± 28	63 ± 57	75 ± 30	42	0
Creatinine clearance (ml/min)	67 ± 23	62 ± 20	65 ± 23	65 ± 23	74 ± 26	45 ± 18	82 ± 24***
Fracture after fall from standing height (n)	80	66	14	na	na	45	35
N of contributors (n)	86	62	24	70	16	na	na
N with contributors (n)	57	40	17	45	12	na	na
N with bone-related fracture risks	54	42	12	44	10	33	21
N with fall-related fracture risks	79	57	22	65	14	46	33
Time Go Up and Go (min)	8.6 ± 7.9	8.4 ± 8.0	8.9 ± 8.0	8.2 ± 8.0	9.8±8.0	8.1±8.6	9.2±7.1
N with MVD <0.80 (n/n measured)	53/93	35/66	18/27	42/73	11/20	36/54	17/39***
N with MVD <0.75	29	22	7	24	11	19	10

*p < 0.05 women vs. men, ** p < 0.05 between fragility fracture and high-energy trauma, *** p < 0.05 between group with and without contributor, Na: not applicable

Characteristics of the Patient Population (N = 100)
Variable Median±SD	All patients	Women	Men	Fragility fracture	High energy trauma	With contributors	Without contributors
Number	100	73	27	80	20	57	43
Women/men (n)	73/27	na	na	66/14	7/13**	40/17	33/10***
Caucasian ethnicity (n)	97	94	27	79	18	55	42
Age (years)	68 ± 10	70 ± 9	62 ± 8*	69,1 ± 9	63.3 ± 9**	71 ± 10	64 ± 7***
Weight (kg)	66 ± 13	63 ± 13	73 ± 11*	65,4 ± 14	68.8 ± 11	64 ± 14	69 ± 11
Spine T-score	-2.88 ± .91	-2.94 ± 0.79	-2.73 ± 1.17	-2.9 ± 0.92	-2.8 ± 0.83	-2.85 ± 0.97	-2.93 ± 0.82
Hip T-score	-1.92 ± 0.9	-2.13 ± 0.92	-1.37 ± 0.70*	-2 ± 0.87	-1.6 ± 1.09	-2.1 ± 1.00	-0.66 ± 0.63***
Hip Z-score	-1.92 ± 0.8	-0.57 ± 0.85	-0.89 ± 0.73	-0.62 ± 0.85	-0.83 ± 0.72	-0.66 ± 0.97	-0.66 ± 0.63
BMD spine(g/sq cm)	0.772± 0.100	0.756 ± 0.085	0.810 ± 0.130*	0.765 ± 0.103	0.795 ± 0.094	0.776 ± 0.109	0.766 ± 0.091
BMD hip(g/sq cm)	0.718± 0.395	0.676 ± 0.115	0.825 ± 0.107*	0.700 ± 0.116	0.779 ± 0.160**	0.695 ± 0.143	0.749 ± 0.106
Calcium intake(mg/day)	852 ± 432	828 ± 448	915 ± 389	851 ± 467	854 ± 266	744 ± 343	993 ± 497***
Serum 25OH vitamin D (nmol/L)	66 ± 53	67 ± 60	63 ± 28	63 ± 57	75 ± 30	42	0
Creatinine clearance (ml/min)	67 ± 23	62 ± 20	65 ± 23	65 ± 23	74 ± 26	45 ± 18	82 ± 24***
Fracture after fall from standing height (n)	80	66	14	na	na	45	35
N of contributors (n)	86	62	24	70	16	na	na
N with contributors (n)	57	40	17	45	12	na	na
N with bone-related fracture risks	54	42	12	44	10	33	21
N with fall-related fracture risks	79	57	22	65	14	46	33
Time Go Up and Go (min)	8.6 ± 7.9	8.4 ± 8.0	8.9 ± 8.0	8.2 ± 8.0	9.8±8.0	8.1±8.6	9.2±7.1
N with MVD <0.80 (n/n measured)	53/93	35/66	18/27	42/73	11/20	36/54	17/39***
N with MVD <0.75	29	22	7	24	11	19	10

*p < 0.05 women vs. men, ** p < 0.05 between fragility fracture and high-energy trauma, *** p < 0.05 between group with and without contributor, Na: not applicable

Laboratory Abnormalities That Required Further Exploration in Men and Women More Than 50 Years of Age With a Recent Clinical Fracture (N = 100)
Laboratory abnormality	Total
Exogenous hypervitaminosis D (>220 nmol/l)	1
Hypercalciuria in 24 hours urine	3
TSH 0.4-3.5 mU/L	13
- >3.5 mU/L	10
- treated hypothyroidism	9
-TSH <0.4 mU/L	1
-TSH >3.5 mU/L	3
- treated hyperthyroidism	3
-TSH >3.5 mU/L	1
-TSH <0.4 mU/L	2
Serum testosterone in men <12 nmol/L (one measurement)	1
Total number of patients	14

Authors and Disclosures

Bianca Dumitrescu,^1,2 Svenjhalmar van Helden,³ Rene ten Broeke,⁴ Arie Nieuwenhuijzen-Kruseman,⁵ Caroline Wyers,⁶ Gabriela Udrea,² Sjef van der Linden,¹ and Piet Geusens ^1,7

¹Department of Internal Medicine, Subdivision of Rheumatology, University Hospital, Maastricht, The Netherlands
²Department of Rheumatology, University of Medicine and Pharmacy 'Carol Davila' Bucharest, Romania
³Department of Trauma Surgery, University Hospital, Maastricht, The Netherlands
⁴Department of Orthopaedic Surgery, University Hospital, Maastricht, The Netherlands
⁵Department of Internal Medicine, Division of Endocrinology, University Hospital, Maastricht, The Netherlands
⁶Epidemiology, Maastricht University, The Netherlands
⁷Biomedical Research Centre, University Hasselt, Belgium

Authors' Contributions: Bianca Dumitrescu analyzed clinical and laboratory data for the diagnosis of contributors to secondary osteoporosis, performed vertebral fracture assessment, statistical analyses and wrote the manuscript. Svenjhalmar van Helden implicated in the coordination of the study, involved in the treatment of patients included in the study, participated to sequence alignment and data presentation. Rene ten Broeke involved in the coordination of the study, involved in the treatment of patients included in the study. Arie Nieuwenhuijzen-Kruseman analyzed clinical and laboratory data for the diagnosis of contributors to secondary osteoporosis, coordinated data presentation. Caroline Wyers gathered laboratory and clinical data, performed statistical analysis. Gabriela Udrea participated in the sequence alignment. Sjef van der Linden analyzed clinical and laboratory data for the diagnose of contributors to secondary osteoporosis, coordinated data presentation. Piet Geusens conceived the study, participated in the design of the study, coordinated the study, analyzed the data for correct diagnosis and drafted the manuscript.

Email: Bianca Dumitrescu - bia1mar@yahoo.com ; Svenjhalmar van Helden - s.vanhelden@surgery.azm.nl ; Rene ten Broeke - rbr@sort.azm.nl ; Arie Nieuwenhuijzen-Kruseman - a.kruseman@intmed.unimaas.nl ; Caroline Wyers - caroline.wyers@epid.unimaas.nl ; Gabriela Udrea - gabiudrea@yahoo.com ; Sjef van der Linden - sli@sint.azm.nl ; Piet Geusens - piet.geusens@scarlet.be

Disclosure: Bianca Dumitrescu received a EULAR (European League against Rheumatism) grant for research in the field of osteoporosis at the University Hospital of Maastricht. This manuscript is part of her PhD thesis work. The authors declare that they have no competing interests.

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