Bone mass in axial spondyloarthritis: A literature review

Table 1 Summary of the cross sectional studies

Ref.	Sample size(M/F)	Mean age(yr)	Menopausal status pre:post	Diseaseduration (yr)	DXAmachine	Dexa site (coefficientvariation %, if available)	Outcome	Conclusion
Devogelaer et al[19]	AS: 70 (60/10)	39	10:0	15.4	Novo	SPA: non dominant radius DXA: L2-4 QCT: 10 patients LS	DXA values at LS was decreased in the male VF: 2.9%	In patients with severe AS, DXA demonstrates normal values due to new bone formation
Donnelly et al[42]	SpA: 87 (62/25) AS: 82.5% PsA: 8%	M: 43.5 F: 44.8	NM	M: 16.3 F: 16.6	Hologic	L1-4 (0.7), FN (1.5), whole body	AS: in early disease LS-BMD decreased, in advanced AS increased Lumbar Spine density lower in M than F VF 10.3%	DXA is doubtful to truly reflect the state of demineralization in the spine and more emphasis should be placed on measures on FN-BMD
Mullaji et al[43]	AS: 33 (27/6): Mild: 22 (16/6) Adv: 11 (11/0)	32.3	0:6	M: Mild: 8.7 Adv: 11.7 F: Mild: 6.8	Norland	Whole body	LS BMD lower in mild and higher in advanced AS than C In Adv. AS, LS BMD higher than mild AS and C HLA-B27: 100% LS, FN and leg BMD decreased in mild AS compared with C in men	The relation between BMD and severity of disease in the axial skeleton may help to explain the etiology and pathogenesis of the spinal deformities and complications of this disabling condition
Singh et al[44]	AS: 14 (14/0)	50	NA	NM	Hologic	AP L1-4, non dominant hip	FT BMD lower than LS Osteopenia at FN: 64%, LS: 36%	Femoral measurements of BMD are superior to lumbar measurements in the detection of osteopenia in patients with AS
Acebes et al[51]	AS: 18 (16/2)	44.7	NM	10.3	Hologic	L2-4, FN	M: OP 0% osteopenia: 53.8% F: OP and Osteopenia 0% HLA-B27: 100%	Osteopenia in AS occurs as a result of high resorption of bone with normal formation
Meirelles et al[50]	AS: 30 (27/3)	37	3:0	17	Hologic	L1-4, PF	LS openia: 23% OP: 27% FT: openia: 55% OP: 31% AS has lower BMD at LS and proximal femur than C	Bone mass loss in AS is better evaluated in the proximal femur, because of almost free of artifacts
Juanola et al[52]	AS: 18 (0/18)	36.7	18:0	15.1	Hologic	L2-4 (0.5), FN (1)	HLA-B27: 94.4% OP: 5.6%, Osteopenia: 11.1% VF: 5.6%	Slight reduction in BMD in premenopausal women with early AS, but the difference was not statistically significant
Mitra et al[3]	AS: 66 (66/0)	37.8	NA	9.9	Hologic	L1-4 (1.4), FN (2.9)	In patients with AS, BMD and T scores were reduced in both LS and FN VF: 16.7% in AS, 2.6% in C	AS patients with mild disease had higher risk of VF compared with the normal population and this increased with the duration of disease
Borman et al[53]	AS: 32 (32/0)	39.1	NA	14.8	Hologic	Lat L1-4 (2.7)	L1-4 T score and BMD similar among AS and C BMD was similar among active and inactive AS VF: 31.2% Osteopenia: 34.3% in AS, 21.8% in C OP: 34.3% in AS, 6.2% in C	The incidence of osteoporosis is high in AS and patients with active disease are have risk for developing osteoporosis
Dos Santos et al[54]	AS: 39 (39/0)	37.6	NA	8.4	Hologic	Whole body	HLA-B27 79.5% AS had bone loss at spine compared with control group 46% of patients with AS had Z score < –1.5 SD	AS is associated with bone loss, mainly concerning the lumbar spine, in patients whose disease is biologically most active
Toussirot et al[13]	AS: 71 (49/22)	39.1	22:0	10.6	Lunar	L2-4 (1), left FN (1.5)	HLA-B27: 84.5 AS: Lumbar osteopenia: 32.4%, OP: 14.1% higher than C Femur: osteopenia: 22.5%, OP: 14.1% higher than C Good correlation between lumbar, femur, total BMD with QUS	AS has decreased lumbar, hip and total body BMD but soft tissue composition was not involved in disease process
Grisar et al[55]	AS: 30 (22/8) PsA: 23 (17/6) ReA: 10 (5/5)	AS: 44.2 PsA: 45.2 ReA: 47.8	NM	AS: 9.2 PsA: 10.4 ReA: 1.3	Hologic	LS and non dominant hip	AS; OP 47%
Speden et al[7]	AS: 66 (0/66)	43.4	50:16	21.1	Hologic	PA L1-4 (1), non-dominant hip (1.8) and Whole body (0.82)	Hip and whole body BMD reduced in AS Femoral neck OP: 6%, osteopenia: 52% in AS and higher than control Lumbar OP: 8%, osteopenia: 18% in AS	Women with AS have lower hip BMD without correlation with disease duration suggesting that low BMD is an early feature of disease
Capaci et al[56]	AS: 73 (49/24)	37.3	NM	11.8	Hologic	L1-4, FT	L BMD similar in mild and advanced AS, F BMD lower in advanced AS In advanced AS osteopenia or OP higher in the total hip than mild AS VF: 5.5% LS Osteopenia or OP: 68.4%-54.3% PF osteopenia or OP: 51.9-91.7 (mild-advanced)	Syndesmophytes and ligament calcification may mask bone loss in LS therefore hip BMD more convenient to asses OP in AS
Jansen et al[14]	AS: 50 (35/15)	52	NM	21	Hologic or Lunar	AP LS, FN	HLA-B27: 88% VF LS: 6% LS openia: 54% OP: 15% FN openia: 72% OP: 20% and 70% of them correctly diagnosed with QUS	The performance of QUS is similar to DEXA in finding patients with osteoporosis-associated fractures Both osteoporosis and fractures are common sequel in AS
Obermayer-Pietsch et al[16]	AS: 104 (71/33)	41	33:0	15	Hologic or Lunar	LS (2.2-0.9), PF (2-1.6) QCT (1)	HLA-B27: 19%-93% OP: 25% In male AS patients FokI genotypes were independent predictors of low BMD	Vitamin D receptor gene may be involved in BMD differences, bone metabolism and inflammatory processes in ankylosing spondylitis
Baek et al[47]	AS: 76 (76/0) mild AS: 59.2% severe AS: 40.8%	28.1	NA	9.4	Lunar	L2-4, PF	BMD and T score at FN and FT lower in severe AS than mild AS but not at LS Osteopenia: 48% in mild AS (more frequently at LS than proximal Femur) and 31% in severe AS	Osteopenia is frequently observed in both severe and mild AS with little mobility limitation Both BMD in severe disease are lower than in mild disease at the FT but not in the lumbar spine, probably due in part to progressing paravertebral calcification during the course of AS
Gilgil et al[48]	AS: 20 (20/0)	25-63	NA	16.7	Norland	PA L2-4 (1), lat L3 (2.7), left FN (1.2)	PA L2-4 BMD similar between groups but lateral L3 and FN BMD reduced in AS No VF Syndesmophytes: 60% PA LS OP: 20% in AS, 15% in C	Lateral L3 DXA is superior to PA DXA in detecting a decrease in BMD in patients with AS
Karberg et al[20]	AS: 103 (66/37) I: < 5 yr (n:27) II: 5-10 yr (48) III: > 10 yr (28)	I: 34.2 II: 38.1 III: 49.1	NM	I: 2.5 II: 7.0 III: 19.7	Hologic	L1-4, FN, radius	HLA-B27: 92.2% Disease duration < 5 yr OP: 11%, 15% (hip, spine) > 10 yr OP: 29%, 4% (hip, spine) DEXA: OP: 24%, 14% and osteopenia: 52%, 31% (hip, spine) DEQCT OP: 11% and openia: 44% (L) pQCT OP: 1% openia: 16% (radius)	Patients with AS already have reduced BMD at the lumbar spine and the femoral neck early in the disease process. In later stage, OP ratio at hip increased but at LS did not increase
Lange et al[8]	AS: 84 (53/31) I: (10/17) II: (12/10) III: (12/3) IV: (19/1)	I: 32 II: 47 III: 45 IV: 56	NM	I: 9 II: 20 III: 21 IV: 32	Lunar	LS (0.9-1), total hip (1.6)	A high decrease in axial bone density could be verified in both initial and advanced stages of the disease (SE-QCT is better) DXA: osteopenia in 5% and OP in 9.2% SE-QCT: osteopenia in 11.8% and osteoporosis in 30.3% HLA-B27: 81.5%-95% VF: 10.7%	In stages of advanced ankylosis in the vertebral region, priority should be given to SE-QCT to detect bone loss, due to the selective measurement of trabecular and cortical bone
Incel et al[45]	AS: 53 (46/7)	39.5	7:0	10.6	Lunar	L2-4, FN	AS patients have lower BMD in LS and FN in both inactive and especially active patients. Osteopenia is 78.3% in early AS Osteopenia or OP is 63.3% in advanced AS	Severe disease and concomitant urolithiasis may increase bone loss and fracture risk especially at the femur neck
Jun et al[28]	AS: 68 (68/0)	30.7	NA	7.2	Hologic	PA L2-4, left Prox Femur	BMD of LS and FN significantly lower than C VF correlated with BMD femur. VF: 16.2%	Measurement of femur BMD may provide useful information to predict the risk of vertebral fractures in patients with AS
Kim et al[24]	AS: 60 (51/9)	31.2	NM	5.5	Hologic	AP L1-4 (1), right FN (1.2)	HLA-B27 83% OP: LS 19%, FN 33% Osteopenia: LS 37%, FN 41% The patients with AS presented reduced BMD and T score at spine	About 74% of AS patients have reduced BMD The imbalance between RANKL and OPG might be involved in the pathogenesis and clinical courses of osteoporosis in AS
Sarikaya et al[57]	AS: 26 (21/5)	44.3	5:0	NM	Hologic	Non dominant hip (1), forearm (1)	Hip BMD values are lower in AS whereas radius BMD values are similar between 2 group Hip Osteopenia or OP: 76.9%	OP at hip region may be due to localized effects of inflammatory activity or immobility rather than a systemic effect
Altindag et al[58]	AS: 62 (36/26)	33.4	NM	5.7	Hologic	AP L2-4, left FN	Lumbar and femoral neck BMD scores are significantly lower in AS OP: 32% osteopenia: 17.7%	Lumbar BMD scores negatively correlated with the length of disease duration in AS patients
Stupphann et al[15]	AS: 21 (10/11)	51	NM	25.4	Lunar	L1-4, total hip	TH: Osteopenia or OP 45% by DXA LS: Osteopenia or OP 48% by QCT QCT and DXA at proximal femur show a significant correlation but not at LS	Activated CD4+ and CD8+ T cells contribute to the production of RANKL in the inflammatory bone-resorption
Ghozlani et al[23]	AS: 80 (67/13)	38.9	13:0	10.8	Lunar	AP L1-4, proximal F	OP: 25% VF: 18.8% OP is common in patients with AS and seems to be related to disease activity	Measuring BMD in early disease should include DXA in the spine and hip. In advanced disease, BMD evaluation should rely on hip DXA
Mermerci Başkan et al[25]	AS: 100 (75/25)	39.9	25:0	10.5	Hologic	AP L1-4 and Lat L2-3, FN	Thoracic VF: 16% Lumbar VF: 3% OP: 32% Acute phase reactant levels of the AS patients with OP are higher than the patients without OP	Vitamin D deficiency in AS may indirectly lead to osteoporosis by causing an increase in the inflammatory activity
Arends et al[22]	AS: 128 (93/35)	41		14	Hologic	AP L1-4, PF	BMD of the lumbar spine, measured by DXA, may be overestimated due to osteoproliferation in patients with advanced AS HLA-B27: 84% VF: 39% Osteopenia or OP: 57%	Bone turnover, inflammation, and low vitamin D levels are important in the pathophysiology of AS-related osteoporosis
Korczowska et al[59]	AS: 66 (66/0)	AS: 51.6	NA	17.4	DTX-200 or ECLIPSE	Forearm and hip	Forearm: Osteopenia: 54% and OP: 14% Hip: Osteopenia: 51% and OP: 5%	Accelerated loss of bone tissue is observed in patients with AS
Vasdev et al[29]	AS: 80 (80/0) C: 160 (160/0)	32.9		8.1	Hologic	LS (1), hip (1)	In active and inactive patients, BMD is similar OP: 28.8% at LS and 11.5% at FN VF: 1.25% HLA-B27: 86%	OP is a significant complication in AS even in early disease, and more prevalent in the spine compared to femur Spinal BMD is the most sensitive site for defining OP in AS
van der Weijden et al[4]	SpA: 130 (86/44) AS: 72% uSpA: 12% PsA: 8%; ReA: 4%	38	42:2	6.3	Lunar	L2-4, left PF	Osteopenia: 38%, OP: 9% HLA-B27: 74% No differences between group for distribution of the osteopenia and OP at hip or LS BMD	A high frequency of low BMD is found in patients with early SpA and it is associated with male gender and decreased functional capacity
Grazio et al[26]	AS: 80 (46/34)	52.3	NM	21.8	Hologic	L2-4, left PF	HLA-B27 86% at LS: OP: 25% and osteopenia: 20% at FN OP: 22.5 and osteopenia: 47.4% More patients with osteopenia at the lumbar spine had lower BASDAI score	Hip BMD seems to be more associated with disease activity and functional ability than BMD at the lumbar spine
Klingberg et al[27]	AS: 204 (117/87)	50	42:45	24	Hologic	AP L1-4 (0.4), lateral L2-4 (0.6), left hip, non-dominant radius	HLA-B27: 87% ≥ 50 yr osteopenia: 43.6 and OP: 20.8% < 50 yr low BMD 4.9% BMD at lateral LS was lower than AP and revealed more OP	OP and osteopenia is common in AS and associated with high disease burden. Lateral and volumetric lumbar DXA are more sensitive than AP DXA in detecting OP
Klingberg et al[60]	204 (117/87)	50	42:45	24	Hologic	AP L1-4, Lat L2-4, non dominant PF and forearm	BMD was significantly lower in the patients with VF HLA-B27: 87% VF: 11.8%	BMD in the femoral neck, total hip, and estimated vertebral BMD show the strongest association with VF
Taylan et al[61]	AS: 55 (48/7)	AS: 36		10	Hologic	PA L2-4, Left femur	BMD at proximal femur is lower but at lumbar spine was similar HLA-B27: 64.9%
van der Weijden et al[62]	SpA: 113 (75/38) AS: 71%	37	38:0	5.7	Lunar	L2-4, left PF	In patients with VF, BMD at LS is lower than patients without VF HLA-B27: 75% VF: 15%	The VFs are associated with low BMD of the lumbar spine and with axial PsA
Akgöl et al[30]	nr-axSpA: 46 (32/14)	31.4	14:0	< 3	Hologic	LS (1), PF (3)	Patients with nr-axSpA have significant bone loss at the lumbar spine compared with patients with mLBP Comparison of BMD in the nr-axSpA subgroups reveal that patients with inflammation had lower BMD at the LS and PF HLA-B27: 60.8%; no VF	Inflammation on MRI is closely associated with low bone mass in patients who are in the very early stage of the disease
Briot et al[21]	SpA: 332 (174/158)	33.8	151:7	1.6	Hologic or Lunar	L1-4, FN, FT	Low BMD associated with presence of inflammatory lesions on MRI, ESR or CRP HLA-B27 62.1% Low BMD: 13% (M: 88%)	Patients with early SpA had 13.0% low BMD and the main risk factor associated with low BMD was inflammation on MRI
Klingberg et al[9]	AS: 69 (69/0)	49	NA	23	Hologic	AP L1-4, lat L2-4, non dominant forearm and hip HRpQCT: radius (0.3-3.9) and tibia (0.1-1.6) QCT: L1-4	The AS patients have lower vBMD in peripheral bone Syndesmophytes are significantly associated with decreasing trabecular vBMD in lumbar spine Estimated lumbar vBMD by DXA correlate with trabecular vBMD measured by QCT HLA-B27 94%	Male patients with AS have axial osteopenia. New bone formation cause false normal BMD at LS by DXA
Ulu et al[46]	AS: 86 (69/17)	AS: 34.5	NM	11.7	Hologic	PA L1-4, lat L2-4, femur	HLA-B27: 66.3% Syndesmophytes: 37.2% VF: 28% PA spine BMD similar with C Lateral spine, hip BMD lower in AS PA BMD higher in late stage AS than early stage FN, FT BMD lat spine BMD similar in two stage	Bone loss increase in AS The BMD measurement at the lateral lumbar spine reflects bone loss and fracture risk better than PA spine and femoral measurements

BMD: Bone mineral density; C: Control; DEQCT: Dual-energy quantitative computed tomography; DXA: Dual energy X-ray absorptiometry; F: Female; FN: Femur neck; FT: Femur total; HRpQCT: High-resolution peripheral quantitative computed tomography; M: Male; mLBP: Mechanic low back pain; NA: Not applicable; NM: Not mentioned; OP: Osteoporosis; PA: Posteroanterior; PF: Proximal femur; pQCT: Peripheral quantitative computed tomography; SE-QCT: Single energy quantitative computed tomography; vBMD: Volumetric BMD; VF: Vertebra fracture; LS: Lumbar spine.

Table 2 Summary of the follow-up studies

Ref.	Sample size(M/F)	Mean age(yr)	Menopausal status(pre:post)	Diseaseduration (yr)	Dexamachine	Dexa site (coefficientvariation %)	Follow-up(mo)	Outcome	Conclusion
Lee et al[17]	AS: 14 (14/0) 7 early AS 7 advanced AS	33.3 54.6	NA	5.4 27	Hologic	LS (1), FN (1)	15	Baseline LS BMD measured by QCT decrease in both early (also by DXA) and advanced diseases and do not change significantly over 15 mo HLA-B27 92.9%	AP LS DXA in late AS is less useful than QCT in determining the degree of osteopenia in late AS
Gratacós et al[6]	AS: 34 (27/7) Active 14 (12/2) Inactive 20 (15/5)	Active: 33 Inactive: 31	7:0	7.5 5.3	Lunar	LS (0.8), FN (2.3)	19	At the end of the follow-up period, patients with active AS show a significant reduction in bone mass in the LS (5%) and FN (3%)	Loss of bone mass only in patients with persistent active AS suggests that inflammatory activity plays a major role in the pathophysiology of the early bone loss
Maillefert et al[32]	AS: 54 (35/19)	37.3	16:3	12.4	Hologic	PA L2-4 (2.8), left FN (4)	24	After 2 yr, BMD did not change at the LS and decreased at the FN The change in BMD at FN was related to persistent systemic inflammation HLA-B27 88.9% VF: 3.7% after 24 mo	Persistent inflammation may be an etiologic factor of bone loss in AS
Kaya et al[31]	AS: 55 (42/13) Active: 22 Inactive: 33	35.8	13:0	11.1	Lunar	AP L2-4 (2.1), PF (2.3)	24	Active AS have lower BMD at PF than inactive ones but LS BMD was similar 0.9% decrease in BMD at FN and increase at LS after follow-up, this change not different in active and inactive AS Active AS OP: PF: 22.7%, LS: 27.3% Osteopenia: PF: 40.9%, LS: 31.8 inactive AS OP; PF: 3%, LS: 21,2% Osteopenia; PF 45.5%, LS: 33.3%	PF measurements seem to be less affected from disease-related new bone formation
Haugeberg et al[33]	SpA: 30 (15/15)	31.1	15:0	6	Lunar	AP L2-4 (2.3), both hip (2.8) and hand (1.1)	12	No significant reduction in BMD at hip, spine and hand is seen after 12 mo follow-up Bone loss at PF is found to be associated with raised baseline CRP levels, baseline BMO of the SIJs on MRI HLA-B27 56.7	Bone loss in patients with SpA is a result of systemic inflammation and starts early in the disease process
Korkosz et al[18]	AS: 19 (19/0)	45.6	NA	16.5	Lunar	L2-4 (1.6-2.2), left hip QCT: L1-5	120	During the follow-up VF: 15.8% In spine, trabecular BMC decrease by QCT whereas BMD increase by DXA	In AS patients, spinal trabecular bone density evaluated by QCT decrease over 10-yr follow-up and it is not related to baseline radiological severity of spinal involvement

AP: Anteroposterior; AS: Ankylosing spondylitis; BMC: Bone mineral content; BMD: Bone mineral density; BMO: Bone marrow edema; DXA: Dual energy X-ray absorptiometry; F: Female; FN: Femur neck; HLA: Human leukocyte antigen; LS: Lumbar spine; M: Male; MRI: Magnetic resonance imaging; NA: Not applicable; NM: Not mentioned; OP: Osteoporosis; PA: Posteroanterior; PF: Proximal femur; QCT: Quantitative computed tomography; SIJs: Sacroiliac joints; VF: Vertebra fracture.

Table 3 Summary of the interventional studies

Ref.	Sample size(M/F)	Mean age	Menopausal statuspre:post	Disease duration(yr)	Dexa machine	Dexa site (coefficientvariation %)	Follow-upduration	Outcome	Conclusion
Allali et al[39]	SpA: 29 (23/6)	35	6:1	13	Hologic	AP L2-4, left PF	6	A significant increase in BMD at the LS, total hip and trochanter is observed in patients with SpA treated with anti-TNF	Benefit of anti-TNFα therapy on BMD in patients with SpA may be through an uncoupling effect on bone cells
Briot et al[37]	SpA: 19 (17/2)	40	NM	16.5	Hologic	L2-4, left FT	12	After 1 yr of treatment BMD increase at the spine and femur total	Treatment with anti-TNFα in SpA is associated with an increase of BMD, which results from a decrease of bone resorption
Biriot et al[41]	SpA: 106 (80/26) AS: 87.8% PsA: 6.6%	38	NM	16.5	Hologic	L2-4, left PF	24	At 1 and 2 yr of treatment, there is a significant gain in BMD at both lumbar spine and PF HLA-B27: 89% Baseline: OP: 28%, osteopenia: 23%	This 2-yr prospective study show a significant increase in BMD, in patients with SpA receiving anti-TNFα treatment
Visvanathan et al[40]	AS: 279 (225/54)	40.3	NM	11.9	NM	L1-4, PF	24	BMD at the spine and hip increase after anti-TNF therapy compared with placebo HLA-B27: 86.7%	Infliximab have positive effect on BMD over 2 yr
Kang et al[34]	AS: 90 (72/18)	29.9 (onset age)	18:0	8.2	Lunar	AP L1-4, right PF	36	The most increase in BMD is observed at the spine and hip in the group treated with concurrent bisphosphonate and anti-TNF HLA-B27: 97% OP: 36.7%	BMD increases more with the combination treatment (bisphosphonate and anti-TNF) and gain of bone mass is associated with the decrease in inflammation
Arends et al[35]	AS: 111 (78/33)	42.2	NM	16	Hologic	AP L1-4, PF	36	LS and hip BMD significiantly increase compared to baseline after anti-TNFα theraphy HLA-B27: 81% LS OP: 9%, openia: 34% TF OP: 2%, openia: 37%	Three years of anti-TNF therapy results increase in bone formation in accordance with the continuous improvement in lumbar spinal BMD
Dischereit et al[38]	RA: 18 (3/15) AS: 16 (9/7)	RA: 62 AS: 48	NM	-	Lunar	AP L2-4 (1.5), FN (2)	24	At baseline in AS, osteopenia: 50% and OP: 6.3% A stable peripheral BMD, significant increases in axial BMD, could be observed after 24 mo of anti-TNFα therapy compared with baseline	Anti-TNF therapy has favorable effects over osteoprotective pathways in patients with AS and RA
Kang et al[36]	AS: 63 (52/11)	36.8	11:2	8.6	Prodigy	L1-4, right PF	24	BMD at LS and FT of patients receiving anti-TNF increase regularly over 2 yr TNF blocking therapy and the increase in SASSS are independently associated with increased BMD at lumbar spine HLA-B27: 87%	TNF inhibitors appear to be associated with increased SASSS scores and improvements in BMD

BMD: Bone mineral density; F: Female; M: Male; FN: Femur neck; FT: Femur total; NM: Not mentioned; PF: Proximal femur; TNF: Tumor necrosing factor; SpA: Spondyloarthritis; AS: Ankylosing spondylitis; SASSS: Stoke Ankylosing spondylitis spine score; PsA: Psoriatic arthritis; RA: Rheumatoid arthritis; TF: Total femur; OP: Osteoporosis; HLA: Human leukocyte antigen; LS: Lumbar spine.

Table 4 Variation of the bone formation and resorption markers

Ref.	Bone formation markers		Bone resorption markers
	bALP	OC	CTX	DPD
Borman et al[53]		Increased
Grisar et al[55]	Increased	Increased	Increased	Increased
Speden et al[7]	Decreased	Decreased		Increased
Sarikaya et al[57]		Decreased		Increased
Lee et al[17]		Normal		Normal
Altindag et al[58]	Increased	Decreased	Increased
Mermerci Başkan et al[25]	Normal
Acebes et al[51]			Normal	Increased

bALP: Bone alkaline phosphatase; OC: Osteocalcin; CTX: C-terminal cross-linking telopeptide of type I collagen; DPD: Deoxypyridinoline.