Hand bone mass in rheumatoid arthritis: A review of the literature

Table 1 Details of the studies included in the systematic reviews

Ref.	Study type	Sample size(M/F)	Mean/Median age	Disease duration (yr)	DXA equipment	DXA site	Coefficient variation BMD	Follow-up duration (yr)	Outcome	Conclusion
Florescu et al[19]	CS	RA: 10 HC: 10	63	15.3	Norland	MC bones (II-V)	0.9%-3.0%		There was a significant correlation between hand BMD and radiographic scoring methods	Hand BMD measurement may be a useful method for the detection and monitor of disease progression
Peel et al[34]	CS	RA: 70 F	64	3-45		WH, LS, femoral neck			Increased bone loss in patients with RA vs controls Hands: 22.7% Lumbar spine: 10.7% Femoral neck: 16.3% Total body: 11.3%	Significant correlation between hand BMD and BMD at other sites. Hand BMD correlated with grip strength and inversely related to ESR in patients with early RA
Deodhar et al[13]	CS	RA: 56 (22/34) Controls: 95 (46/49)	M: 64 F: 64	9	Hologic	WH	1%-3%		Mean total hand BMC (grams, M/F) RA: 81.7 /52.3 Controls: 90.9/62.2	Hand BMC correlated with disease severity but not with disease activity
Devlin et al[3]	CS	RA: 202 (61/141)	M: 59 F: 53	M: 1.6 F: 1.9	Lunar	LS Hip WH	0.6%		Hand BMD correlated with disease activity, functional capacity, lumbar and hip BMD	Hand bone loss can be used as outcome measure
Njeh et al[30]	CS	RA: 51 F Patients with osteopenia: 44 F HC: 52 F	Mean age 57.5		Lunar DPX-L	LS, Hip, WH			Mean Hand BMD (g/cm2) in patients with RA: 0.415	Hand BMD was correlated with phalangeal ultrasound and hand functions but not CRP or ESR
Ozgocmen et al[22]	CS	RA: 30 F HC: 29 F	45.5		Lunar	WH II MC LS Hip	-		CI and C: MC ratio correlated with II. MC midshaft and hand BMD	CI may predict cortical bone mass of the hand. C: MC ratio is a useful method for evaluating progression of wrist involvement
Alenfeld et al[14]	CS	RA: 41 (18/23) HC: 103 (35/68)	54	F: 2.1 M: 2	Lunar	WH Subcondral ROI	WH: 0.9 subcondral region: 2.7%-3.2%		Hand bone loss in the subregional regions is higher than total hand BMD	In early RA periarticular osteoporosis may be better assessed using detailed hand scan analyses
Ardicoglu et al[18]	CS	RA: 49 (9/40) HC: 34 (5/29)	49.1	5	Lunar	LS Hip WH			Hand BMD correlated with disease duration, CRP and radiographic scores	Hand BMD by DXA is a useful pratical and reproducible method
Harrison et al[20]	CS	RA: 17 (4/13) PsA: 15 (9/6)	RA:51 PsA:53	RA: 31 PsA: 27	Hologic	MCP, PIP, DIP joints	3.4%-6.6%		Periarticular BMD was significantly lower in patient with RA than PsA Periarticular BMD correlated with the number of swollen, tender joints in RA	Periarticular osteoporosis is associated with joint inflammation in RA but not PsA
Ozgocmen et al[47]	CS	RA: 15 F HS: 3 F	48.5	6.8	Lunar	WH, MCP	-		Flow patterns correlated with intra-articular bone and cartilage destruction	PDUS is a useful method for monitoring disease activity and measurement of therapeutic response
Jensen et al[48]	CS	RA: 11 female	53		Hologic	MC bones, forearm	0.65%-0.83%		There was a significant association between DXA-BMD and DXR-BMD	Periarticular bone loss can be detected better and earlier with DXR than DXA in patients with RA
Castañeda et al[15]	CS	EA: 22 (2/20) HC: 16 (3/13)	EA: 48.4 HC: 49.2	0.4	Hologic	WH MCP	MCP: 1.3% -0.7% WH: 1.4 %-0.9%		Whole hand BMD: (g/cm2) HC: 0.355 EA: 0.349 MCP BMD: (g/cm2) HS: 0.295, EA: 0.285	Measurement of BMD at MCP joints may be a useful method to assess the diagnosis or prognosis in patients with EA
Franck et al[21]	CS	RA: 421 (64/357) HC: 98 (31/67)	M: 56.11 F: 58.4	M: 4.8 F: 4.8	Hologic	LS, hip, forearm, WH, MCP II-III	Subregional scans: 0.9%-1.4% for short term, 1.5%-2.3% for mid-term		There was a significant correlation between WH BMD and its subregions, hip and forearm. Subregional BMD was correlated with CRP, bone resorption markers and grip strength	Measurement of hand and subregional BMD by DXA is accurate and reproducible method in RA
Murphy et al[49]	CS	RA: 4 SpA: 3	36.7	1.25	Hologic	MCP/PIP	0.73%-0.78%		The precision of MCP joints was greater than PIP joints	DXA can be used as a reliable measure for periarticular BMD
Alves et al[16]	CS	Established RA: 25 EA: 25 HS: 37	Established RA: 53 Early arthritis: 52		Lunar	WH, LS, hip, MCP and/or PIP joints mid MC to mid-phalangeal	0.45%-1.07%		Mean BMD of five ROI: Established RA: 0.321 to 0.372 Early arthritis: 0.321 to 0.382 HC: 0.342 to 0.401 Mean BMD of whole hand: Established RA: 0.387 Early arthritis: 0.392 HC: 0.420	Measurement of periarticular BMD is not a useful tool to discriminate between patients with early RA from HC
Zhu et al[7]	CS	RA: 100 F	53.4	9.1	Hologic	LS, hip, ultradistal radius			BMD assessed by HR-pQCT significantly correlated wth BMD at the peripheral and central skeleton	HR-pQCT is a useful method for evaluating periarticular bone loss at both cortical and trabecular bone
Moon et al[17]	CS	RA: 45 HC: 106	47.5		Lunar	Shaft and periarticular region of PIP, LS, hip			The ratio of shaft to periarticular BMD was higher in patients with RA	DXA assisted localized quantification and BMD ratio calculations are useful for assessing periarticular osteoporosis in early RA
Dogu et al[33]	CS	RA: 83	52.9	6.99	Lunar	WH	-		Hand BMD was correlated with HGS, TTP, radiological erosions but not DHI	HGS and TTP were most effective indicator of hand function
Deodhar et al[10]	LS	RA: 81 (33/48) HC: 95 (46/49)	Early RA: M: 53, F: 55 Late RA M: 65.5, F: 63	Early RA: 0.8 Late RA: 9	Hologic	WH		1	After 1 yr hand bone loss Early RA: M: 3.25%, F: 1.46% Late RA, no significant loss of hand BMD	Hand bone loss was highest in patients with early RA and correlated with disease activity
Daragon et al[25]	LS	Early RA: 15 (6/9) Other rheumatic diseases: 15 (7/8)	Early RA:42.7 Other rheumatic diseases: 48.8	0.4	Hologic	WH		1	There was no significant correlation between hand bone loss and clinical, radiological and biological parameters except for IFN alfa	Hand BMD by DXA may be useful tool for the early classification of inflammatory disease
Deodhar et al[26]	LS	Early RA: 40	-	< 2	Hologic	WH	2.3%	5	Percent change in BMD after 1 yr: -5.5, 2 yr: -7.5, 3 yr: -9.8, 4 yr: -9.9, and 5 yr: -10	Early loss in hand BMD (in the first six months) may be a prognostic marker for disease activity, functional status or poor functional outcome
Berglin et al[31]	LS	RA: 43(13/30)	Not available	0.6	Lunar	WH		2	Hand bone loss correlated with radiographic progression	Hand bone loss and radiographic progression were retarded by early treatment
Jensen et al[24]	LS	RA: 51 (10/41) Unclassified polyarthritis: 21 (3/18)	RA: 54 Unclassifiesd polyarthritis: 39	0.3	Norland	MCP, forearm		2	Hand BMD decreased only in patients with RA and associated with disease activity	DXR is better than DXA for detecting and monitoring periarticular osteoporosis of the MC bones
Haugeberg et al[4]	LS	Undifferentiated arthritis: 74 (9/65)	65	0.5	Lunar	LS Hip	1.07%	1	At the 1 yr follow-up, hand BMD loss; RA: -4.27 Inflammatory non-rheumatoid group: -0.49 Non-inflammatory group: -0.87	Hand DXA may be useful for determining the risk of progressive disease in RA
Haugeberg et al[36]	LS	RA: 79 (32/47)	49.7	0.7	Lunar	WH		0.9	Mean hand BMD loss 2.5% at 24 wk, 2.6% at 48 wk	Hand DXA is more sensitive than radiology can be used as outcome measure in early RA
Murphy et al[23]	LS	RA: 20 (8/12) SpA: 18 (11/7)	RA: 37, SpA: 33	RA: 0.4 SpA: 0.4	Hologic	WH LS Hip		1	Periarticular bone loss correlated with radiographic damage, disease activity and baseline TIMP-1 level	TIMP-1 may be use as a biomarker of periarticular bone loss in early RA
Hill et al[27]	LS	RA: 50 (12/38) Control: 30	57	0.75	Lunar	WH, LS, hip	1.1%	1	Hand BMD correlated with baseline CRP and radiographic score in RA	Hand BMD using DXA is a safe, reproducible procedure. It may predict radiological progression and disease activity
Bejarano et al[35]	LS	RA: 64 (27/37)	54.1	0.5		WH, lumbar spine, hip		6.4 yr	Follow-up change in hand BMD, -0.034	First year hand BMD loss was not associated with function or quality of life status but not long-term radiographic progression
Naumann et al[28]	LS	Early RA: 17 (4/13) Established RA: 35 (8/27)	Early RA: 55, Established RA with moderate disease activity: 58 Established RA with high disease activity: 53.5	Early RA: 0.2	Lunar	WH, MCP/ PIP, wrist, LS hip	Wrist: 0.75 WH: 0.78	1	There was a negative correlation between hand BMD and MCP joint synovitis in patients with high diasease activity. The best precision values of BMD were found for the wrist	Hand BMD measurement by DXA is highly reproducible method in patients with RA
Black et al[37]	LS	RA: 106 (29/77)	57	0.3	Lunar	WH		1	Lower hand BMD was associated with higher erosion scores	Hand BMD loss in the first 6 mo can predict early erosive change in patients with early RA
Haueberg et al[38]	IS	RA: 20 (7/13) IFX + MTX: 10	52.2	< 1	Lunar	WH, LS, hip		1	BMD (gr/cm2) IFX treated group: WH: 0.42, spine: 1.14, T hip: 1.04, F neck: 1.03 Placebo: WH: 0.43, spine: 1.28, T hip: 1.06, F neck: 1.01	In the IFX treated group hand bone loss arrested at the hip but not at the hand and lumbar spine
Deodhar et al[39]	IS	Placebo: 13 Denosumab 60 mg treated group: 21 (7/14) Denasumab 180 mg treated group: 22 (5/17)	Placebo: 55.2 Denosumab 60 mg treated group: 57.7 Denasumab 180 mg treated group: 58.7	Placebo: 10.3 Denosumab 60 mg treated group: 12.6 Denasumab 180 mg treated group: 15.8	Lunar	WH		1	Mean change in hand BMD at 6/12 mo (%); denosumab 60 mg: 0.8/1 Denosumab 180 mg: 2/ 2.5 placebo: -1.2/-2	Denosumab increased hand BMD and decreased progression of bone erosion in RA
Haugeberg et al[29]	IS	MTX group: 19 (10/9) MTX + IAST: 21 (8/13)	MTX group: 56.2 MTX + IAST: 53.3	MTX group: 0.5 MTX + IAST: 0.4	Lunar	WH, MCP, hip, LS		1	In the first 3 mo, hand bone loss was lower in MTX + IAST treated group than MTX treated group. Hand bone loss associated disease activity, hand function and MRI synovitis score	IAST may protect against periarticular bone loss in inflamed finger joints in RA
Szentpetery et al[32]	IS	RA: 35 (11/24) PsA: 27 (12/15)	RA: 56 PsA: 44	RA: 8 PsA: 7	Hologic	WH, PIP/MCP, hip, LS		3	Following anti- TNF therapy hip BMD decreased but spine and hand BMD unchanged. Periarticular BMD around PIP joints increased, MCP decreased	Anti TNF therapy increased bone formation without a change in bone resorption

CS: Cross-sectional study; CI: Cortical index; MC: Carpo:metacarpal; EA: Early arthritis; DXR: Digital X ray radiogrammetry; DXA: Dual X ray absorptiometry; HR-pQCT: High-resolution peripheral quantitative computed tomography; HGS: Handgrip strength; IAST: Intra-articular corticosteroid; HC: Healthy controls; IS: Interventional study; LS: Longitudinal study; PsA: Psoriatic arthritis; ROI: Region of interest; RA: Rheumatoid arthritis; SpA: Spondiloartropathy; TIMP-1: Tissue inhibitor of metalloproteinases 1; TTP: Three-finger pinch; vBMD: Trabecular volumetric bone mineral density; WH: Whole hand; LS: Lumbar spine; BMC: Bone mineral content; BMD: Bone mineral density; EA: Early arthritis; MTX: Methotrexate.